Nevin Manimala

Clin Chem Lab Med. 2026 Apr 20. doi: 10.1515/cclm-2026-0435. Online ahead of print.

ABSTRACT

OBJECTIVES: Large language models (LLMs) show promise for interpreting laboratory reports, yet real-world validation remains limited. This study evaluated five advanced LLMs in interpreting urinalysis reports for kidney diseases using real-world clinical data, providing empirical evidence for the utility of LLM-assisted result interpretation.

METHODS: We retrospectively collected 120 urinalysis reports from patients with primary glomerular diseases and secondary nephropathies. The testing platforms included the Sysmex UF5000 and Mindray EU8600. Five LLMs (ChatGPT-5, Claude-4.5, Gemini-2.5, DeepSeek-V3.1, Qwen-3) were tasked with interpreting reports across five functional dimensions. Four certified laboratory technologists and four licensed physicians evaluated outputs using a 5-point Likert scale across six quality dimensions. Statistical analyses employed Friedman and Wilcoxon signed-rank tests.

RESULTS: All five LLMs demonstrated clinical utility in interpreting urinalysis reports. Proprietary LLMs achieved higher overall scores (Claude-4.5: 4.78 ± 0.47; ChatGPT-5: 4.73 ± 0.50; Gemini-2.5: 4.69 ± 0.54) compared to open-source LLMs (DeepSeek-V3.1: 4.58 ± 0.66; Qwen-3: 4.57 ± 0.69). Across functional dimensions, the models performed proficiently in identifying abnormal parameters and analyzing their correlations, but suboptimally in interpreting instrument flags. Instrument-dependent variability was observed (Sysmex vs. Mindray, p<0.001). In quality assessments, Claude-4.5 exhibited the best overall performance, ChatGPT-5 excelled in accuracy and clarity, and Gemini-2.5 demonstrated strong practicality. Regarding safety, Claude-4.5 exhibited the lowest hallucination rate (7.5 %). Common hallucinations included misinterpretation, definition errors, and over-interpretation.

CONCLUSIONS: LLMs demonstrate significant capability in urinalysis interpretation, though proprietary models currently excel in reasoning and hallucination resistance. Instrument-specific flag interpretation and hallucination mitigation remain critical challenges requiring Retrieval-Augmented Generation (RAG) integration and human oversight.

PMID:42033087 | DOI:10.1515/cclm-2026-0435

Cancer Med. 2026 May;15(5):e71837. doi: 10.1002/cam4.71837.

ABSTRACT

BACKGROUND: Allostatic load (AL) reflects the cumulative physiological burden of chronic stress across cardiovascular, metabolic, immune, and renal systems. While AL has been implicated in cancer development, evidence in Asian populations remains limited. We examined sociodemographic and lifestyle factors of AL and its association with colorectal cancer (CRC) risk in a multiethnic Asian cohort.

METHODS: Data were drawn from 30,443 Chinese, Malay, and Indian adults (≥ 18 years) between 2004 and 2016. Participants were followed from baseline assessment until CRC diagnosis, death, or end of follow-up, whichever occurred first (median follow-up: 7.2 years). AL was derived from nine biomarkers, with high-risk cutoffs set at the 75th percentile (≤ p25 for HDL). High AL was defined as a score ≥ 3. CRC incidence was ascertained through linkage with the Singapore Cancer Registry. Modified Poisson regression was used to identify factors associated with high AL, and Cox proportional hazards models assessed associations with incident CRC. CRC incidence was ascertained through linkage with the Singapore Cancer Registry.

RESULTS: During follow-up, 162 CRC cases were observed; 60.3% of participants had high AL. Older age, male sex, Malay and Indian ethnicity, lower education, unemployment, diabetes, low physical activity, and prolonged sitting were significantly associated with higher AL scores. High AL was associated with increased CRC risk after adjustment for age, sex, ethnicity, and cohort (aHR = 1.53; 95% CI = 1.10, 2.14). The association remained similar in models additionally adjusting for SES, smoking, history of diabetes, or physical activity and sitting time.

DISCUSSION: These findings are consistent with prior research in Western populations and highlight AL as a potential biomarker for identifying individuals at increased CRC risk. Incorporating AL into population health strategies may support earlier detection and targeted prevention in Asian settings.

PMID:42033061 | DOI:10.1002/cam4.71837

Physiol Rep. 2026 Apr;14(8):e70887. doi: 10.14814/phy2.70887.

ABSTRACT

Heart rate variability (HRV) is widely used to assess cardiac health, yet uncertainty persists regarding HRV variations across the menstrual cycle and their association with reproductive hormones. Few studies have evaluated the full spectrum of HRV parameters, and most estimated menstrual phases from the last menstrual period without considering individual cycle length. This study aimed to compare HRV parameters across three menstrual phase groups, using accurate cycle tracking based on the next menstrual period and actual cycle length, and to correlate HRV with estradiol, progesterone, and the estradiol/progesterone (E/P) ratio. In 112 healthy women with regular cycles, HRV parameters were measured using a heart rate sensor, and serum hormone levels were obtained. Menstrual phase groups were defined using back-extrapolation from the next cycle. Data from 99 participants were analyzed: menstruation (n = 38), periovulatory (n = 30), and premenstrual phase (n = 31). HF was significantly higher during the peri-ovulatory phase, while estradiol and progesterone peaked premenstrually. The E/P ratio was highest pre-ovulatory. Estradiol correlated with most HRV measures; however, only the mean RR-interval in the premenstrual phase was statistically significant, with estradiol emerging as a negative independent predictor. These findings conclude notable HRV variation across menstrual phases and suggest that estradiol fluctuations may influence autonomic regulation.

PMID:42033060 | DOI:10.14814/phy2.70887

Angew Chem Int Ed Engl. 2026 Apr 24:e2407356. doi: 10.1002/anie.2407356. Online ahead of print.

ABSTRACT

Infrared nonlinear optical (NLO) materials are essential for laser and photonic technologies, limited by fragmented material systems, lengthy development cycles, and trial-and-error synthesis. To overcome these barriers, we developed an integrated computational-experimental framework integrating first-principles high-throughput calculations, machine learning, and targeted synthesis. We establish a multidimensional properties dataset of 1807 non-centrosymmetric compounds and define a comprehensive figure of merit (CFOM) Q based on the statistical average of this dataset to quantify performance trade-offs. Multidimensional statistical analysis uncovers composition-structure-performance relationships, and reveals superior structure and chemical compositions governing enhanced NLO performance. A Q-based crystal graph neural network classifier is developed, achieving strong predictive accuracy (AUC = 0.95). We identify 12 unreported candidates (Q > 2) from 5105 compounds combining high-throughput calculation and machine learning. Experiments confirm that defect-chalcopyrite HgAl₂Q₄ (Q = S, Se, Te) shows wide band gaps (1. 55-2.82 eV), suitable birefringence (0.06-0.08), and strong NLO responses (2.2-5 × AGS). This work provides an effective pathway for accelerating the discovery of high-performance optoelectronic materials.

PMID:42033040 | DOI:10.1002/anie.2407356

Cancer Med. 2026 May;15(5):e71849. doi: 10.1002/cam4.71849.

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) screening rates remain below recommended clinical guidelines, especially among people of color. This study aimed to assess CRC screening rates, identify barriers, and develop improvement strategies in racially diverse communities using community-based participatory design, engaging Community Health Action Teams (CHATs).

METHODS: This mixed-methods study employed surveys and focus groups, with data collection instruments co-designed with community members to ensure relevance and accuracy. A random sample of households with screen-eligible residents received a survey, focusing on assessing screening rates and identifying facilitators and barriers to CRC screening. Focus groups used snowball sampling in the same communities to deepen understanding through qualitative insights.

RESULTS: Of 1,798 survey respondents, 81% reported participating in CRC screening, with 69% being up to date. Awareness of CRC’s preventable and treatable nature, when detected early, (b = 0.647, p < 0.001, OR = 1.91); understanding its asymptomatic potential (b = 0.345, p < 0.001, OR = 1.42); and recognition of its ranking as the second most deadly cancer (b = 0.354, p = 0.007, OR = 1.42) were significant predictors of screening adherence. Knowledge of at-home tests increased compliance with screening (b = 0.752, p < 0.001, OR = 2.12). Barriers reported by unscreened respondents included a lack of symptoms (19%), absence of motivation (19%), being asymptomatic (20%), and for insured individuals, a lack of physician orders for screening (19%). Insights from focus groups, including 65 participants, revealed multi-level barriers, echoing survey findings where relationships with medical providers emerged as the strongest predictor of screening participation.

CONCLUSIONS: The study informed the creation of six key outreach messages and two strategies co-led by CHATs, emphasizing CRC screening importance, test options, and cost considerations. Suggested strategies include organizing community events to raise awareness and enhancing direct provider-to-patient communication to encourage screening uptake.

PMID:42033015 | DOI:10.1002/cam4.71849

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Dec 28;50(12):2407-2416. doi: 10.11817/j.issn.1672-7347.2025.250455.

ABSTRACT

OBJECTIVES: Ileal conduit diversion is currently the most commonly used urinary diversion method for patients undergoing radical cystectomy. Because intestinal reconstruction is involved, perioperative enteral nutrition intake is limited, placing patients at risk of malnutrition and affecting postoperative recovery and quality of life. Whole-process perioperative nutritional management is of great significance for promoting rapid postoperative recovery in such patients. This study aims to explore the effects of whole-process nutritional management intervention based on the information-knowledge-attitude-practice (IKAP) theory on nutritional status and quality of life in patients undergoing radical cystectomy for bladder cancer.

METHODS: A total of 69 patients who underwent radical cystectomy with ileal conduit diversion for bladder cancer in the Department of Urology, Third Xiangya Hospital of Central South University, between January 2022 and December 2024 were included. Patients were grouped according to admission time. Patients admitted between January 2022 and October 2023 were assigned to the control group (n=34) and received routine perioperative nutritional support for radical cystectomy with ileal conduit diversion. Patients admitted between November 2023 and December 2024 were assigned to the intervention group (n=35) and received whole-process nutritional management based on IKAP theory. Nutritional Risk Screening 2002 (NRS2002) score, Onodera’s prognostic nutritional index (OPNI), and the third edition Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQ-C30) were compared between the 2 groups at 3 time points: day 1 after admission, 1 day before discharge, and 1 month after discharge. The incidence of postoperative related complications between the two groups was also compared.

RESULTS: In both groups, the NRS2002 score at 1 month after discharge was lower than that at 1 day before discharge, and the intervention group had lower scores than the control group, with statistically significant differences (all P<0.05). The OPNI at 1 month after discharge was significantly higher than that at 1 day before discharge in both groups, and the intervention group had higher values than the control group, with statistically significant differences (all P<0.05). There was no statistically significant difference in the incidence of postoperative related complications between the 2 groups (all P>0.05). The EORTCQLQ-C30 scores in the intervention group were higher than those in the control group at 1 day before discharge and 1 month after discharge, with statistical significant differences (both P<0.05).

CONCLUSIONS: Whole-process nutritional management based on IKAP theory can improve the nutritional status and prognosis of patients undergoing radical cystectomy with ileal conduit diversion and improve their quality of life.

PMID:42033000 | DOI:10.11817/j.issn.1672-7347.2025.250455

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Dec 28;50(12):2392-2398. doi: 10.11817/j.issn.1672-7347.2025.250276.

ABSTRACT

OBJECTIVES: Glottal insufficiency can lead to persistent hoarseness and aspiration, and some patients require surgical intervention. Vocal fold injection can improve glottic structure, but the effect of postoperative voice therapy on voice quality remains to be evaluated. This study aims to analyze the clinical efficacy of vocal fold injection with fat and rectus abdominis fascia combined with voice training in the treatment of glottal insufficiency.

METHODS: Clinical data of 15 patients with glottal insufficiency treated in the Department of Otolaryngology-Head and Neck Surgery of the Second Affiliated Hospital of Nanchang University from August 2018 to December 2024 were retrospectively collected. Patients received injection of fat and rectus abdominis fascia into the middle portion of the paralyzed vocal fold, and voice training was initiated 2 weeks after surgery. Patients were evaluated and followed up before surgery and at 3, 6, and 12 months after surgery. The primary outcome indicator was the change in glottal gap. Secondary outcome indicators included voice acoustic parameters, including maximum phonation time (MPT), normalized noise energy (NNE), shimmer, and jitter, as well as the Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale score.

RESULTS: In all treated patients, the injected vocal fold was fuller than before surgery, and no leakage of injected material occurred. The injected vocal fold appeared thickened and shifted medially. Hyperemia and edema were observed within 1 week after surgery, and redness and swelling subsided after 2 months. Compared with before treatment, glottal gap, NNE, shimmer, jitter, and GRBAS scores were significantly reduced at 3, 6, and 12 months after treatment, while MPT was significantly prolonged, with statistically significant differences (all P<0.05). With the increase in the number of voice training sessions, the therapeutic effect became more significant. No patient required secondary vocal fold injection during the 12-month follow-up period.

CONCLUSIONS: Vocal fold injection with fat and rectus abdominis fascia combined with voice training can improve glottal closure and voice quality in patients with glottal insufficiency during short- and mid-term follow-up, and is a feasible treatment.

PMID:42032998 | DOI:10.11817/j.issn.1672-7347.2025.250276

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Dec 28;50(12):2378-2391. doi: 10.11817/j.issn.1672-7347.2025.250190.

ABSTRACT

OBJECTIVES: Sepsis is a highly heterogeneous syndrome. This study aims to identify potential phenotypes of sepsis based on commonly used clinical inflammatory parameters and to investigate the impact of vitamin C infusion therapy on survival outcomes in patients with different phenotypes.

METHODS: Patients with sepsis in the Intensive Care Medical Information Database IV were used as the study population, and the data were randomly divided into two groups of 7:3, which were used for derivation and validation, respectively. In the derivation cohort, the K-means clustering was employed to identify potential phenotypes based on three key feature parameters: white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and temperature, and then assess the effect of infused vitamin C treatment on survival outcomes of each phenotype by Kaplan-Meier survival analysis and multifactorial Cox proportional risk model. The same analyses were used in the validation cohort to verify the clustering effect and the heterogeneity of vitamin C efficacy on each phenotype.

RESULTS: A total of 3 771 patients were included in the final analysis, 2 639 in the derivation cohort and 1 132 in the validation cohort. In the derivation cohort, patients with sepsis were categorized into three phenotypes: cluster A (n=471, 17.8%) was characterized by moderately elevated white blood cells (WBC), neutrophil-to-lymphocyte ratio (NLR), and hyperthermia; cluster B (n=1 812, 68.7%) was characterized by mildly elevated WBC, NLR, and essentially normal body temperature, and patients with this type had the relatively best clinical status and survival prognosis, and cluster C (n=356, 13.5%) was characterized by extreme elevation of WBC and NLR, and insignificant elevation of body temperature, and patients with this type had the most severe organ dysfunction and high mortality. Significant differences in age, vital signs, history of comorbidities, laboratory tests, pathophysiological scores and clinical prognosis were found between phenotypes and showed different responsiveness to vitamin C treatment (all P<0.05). A Kaplan-Meiersurvival analysis showed that intravenous vitamin C infusion was associated with a lower risk of death at 28 days only in patients with cluster A [hazard ratio (HR)=0.388, 95% confidence interval (CI) 0.166 to 0.906, P=0.023], and this protective effect remained statistically significant after correction for confounders by multivariate Cox regression (HR=0.353, 95% CI 0.165 to 0.755, P=0.007), whereas a beneficial effect of vitamin C on survival outcomes was not detected in the other phenotypes. This heterogeneous response yielded similar results in the validation cohort.

CONCLUSIONS: This study identified three distinct sepsis phenotypes with different clinical characteristics based on three key parameters: WBC, NLR, and temperature. Each phenotype exhibits varying responsiveness to vitamin C therapy, with patients with type A sepsis benefiting from intravenous vitamin C treatment.

PMID:42032997 | DOI:10.11817/j.issn.1672-7347.2025.250190

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Dec 28;50(12):2312-2324. doi: 10.11817/j.issn.1672-7347.2025.240565.

ABSTRACT

OBJECTIVES: 16S rRNA gene sequencing is an important method for studying microbial structure in samples. However, whether selecting different hypervariable regions for sequencing in the same sample affects the results remains unclear. This study aims to compare the sequencing results of 16S rRNA gene hypervariable regions V3 to V4 and V4 in children with obesity-related non-alcoholic fatty liver disease (NAFLD), and to provide evidence for scientifically evaluating gut microbiota detection results in obese children with NAFLD.

METHODS: Obese children with NAFLD and children with simple obesity who visited Hunan Children’s Hospital between January 2019 and September 2021 were selected as study subjects. Fecal samples were collected, and total DNA was extracted. After PCR amplification of the gut microbiota V3 to V4 region and V4 region, sequencing was performed. α-diversity, β-diversity, and microbial community structure differences between the 2 hypervariable regions were compared. Seven samples were selected for metagenomic sequencing as the gold standard to evaluate the performance of V3 to V4 and V4 region sequencing.

RESULTS: A total of 145 participants were included, including 92 in the case group and 53 in the control group. The number of operational taxonomic units (OTUs) obtained by V3 to V4 sequencing (16 977) was higher than that obtained by V4 sequencing (3 362). α-diversity analysis showed that in the overall population, the Shannon index (5.49±1.11) and Chao1 index (1 843.04±580.78) in the V3 to V4 region were higher than the Shannon index (4.98±0.65) and Chao1 index (379.59±47.27) in the V4 region (all P<0.001). β-diversity analysis showed overall differences in microbial community structure between the V3 to V4 and V4 regions, and the intergroup differences were greater than the intragroup differences (P<0.05). Welch’s t-test results showed that in the overall population, the numbers of differential taxa detected by V3 to V4 and V4 sequencing at the phylum, class, order, family, and genus levels were 2, 9, 35, 33, and 72, respectively; in the case group, the numbers were 1, 9, 32, 35, and 66; and in the control group, the numbers were 0, 7, 27, 21, and 0. Linear discriminant analysis effect size (LEfSe) analysis showed that V3 to V4 sequencing identified 29 differential taxa between the case group and control group, whereas V4 sequencing identified 7 differential taxa. Sensitivity analysis showed that the Shannon index obtained by V3 to V4 sequencing (5.41±1.62) was not significantly different from that of metagenomic sequencing (6.39±0.42) (P=0.169), while the Chao1 index (1 889.92±781.73) was lower than that of metagenomic sequencing (3 092.71±505.89), with a statistically significant difference (P<0.01). The Shannon index and Chao1 index obtained by V4 sequencing were both lower than those of metagenomic sequencing, with statistically significant differences (4.89±0.94 vs 6.39±0.42, 362.41±35.22 vs 3 092.71±505.89, respectively, both P<0.01).

CONCLUSIONS: Sequencing of the V3 to V4 and V4 regions of the 16S rRNA gene affects the results of gut microbiota structure analysis in obese children. The V3 to V4 region is more likely to detect differential taxa between case and control groups and provides a more accurate estimation of α-diversity. It may therefore be considered a preferred region for gut microbiota sequencing in children with NAFLD. However, there is currently no unified standard for selecting V regions in 16S rRNA gene sequencing, and the detection region and method should be selected comprehensively according to research objectives and sample characteristics.

PMID:42032992 | DOI:10.11817/j.issn.1672-7347.2025.240565

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Dec 28;50(12):2277-2289. doi: 10.11817/j.issn.1672-7347.2025.250566.

ABSTRACT

OBJECTIVES: Practice related to the traditional postpartum confinement custom “Zuo Yuezi” vary among individuals, and its relationship with postpartum depression (PPD) remains unclear. This study aims to explore the current practice and heterogeneity of “Zuo Yuezi” among Chinese women and to analyze its association with PPD.

METHODS: A cross-sectional study was conducted among 542 women from 3 hospitals between January and February 2016. Data were collected on whether participants practiced “Zuo Yuezi”, their willingness and attitudes toward “Zuo Yuezi”, demographic characteristics, adherence to specific “Zuo Yuezi” practices, emotional experiences during the “Zuo Yuezi” period, and PPD symptoms. Latent profile analysis (LPA) was used to identify heterogeneity in “Zuo Yuezi” practices, and multivariate logistic regression was used to analyze the association between practice patterns and PPD.

RESULTS: A total of 542 postpartum women completed the survey. About 98% (531/542) of participants reported practicing “Zuo Yuezi”, among whom 41.2% followed traditional customs and 29.5% followed parental advice. Approximately 95% of women practiced “Zuo Yuezi” for ≥30 days, and nearly half strictly followed a 30-day “Zuo Yuezi” period. Significant heterogeneity was observed in practice components and adherence levels, with the greatest heterogeneity in dietary practices and the lowest in hygiene practices. Latent profile analysis identified 4 levels of adherence to “Zuo Yuezi” practices: low, medium-low, medium, and high. Higher adherence was associated with belief in disease prevention, home-based “Zuo Yuezi” practices, and longer “Zuo Yuezi” duration. Lower adherence was associated with an increased risk of PPD (χ²=16.103, P<0.05).

CONCLUSIONS: The practice of “Zuo Yuezi” is widespread but heterogeneous. Lower adherence to “Zuo Yuezi” practices may increase the risk of postpartum depression, highlighting the need for culturally sensitive and individualized perinatal care.

PMID:42032989 | DOI:10.11817/j.issn.1672-7347.2025.250566