Nevin Manimala

Genet Med. 2026 Jun 19:102632. doi: 10.1016/j.gim.2026.102632. Online ahead of print.

ABSTRACT

PURPOSE: Biallelic variants in the minor spliceosomal gene RNU4ATAC were successively identified in Taybi-Linder/MOPD1 (Microcephalic osteodysplastic primordial dwarfism type I), Roifman, and Lowry-Wood syndromes, characterized by variable microcephaly, short stature, neurodevelopmental impairment, skeletal dysplasia, and immunodeficiency. Two-thirds of the reported individuals present with Taybi-Linder syndrome, the first described and most severe form.

METHODS: We collected clinical and molecular data from individuals with biallelic RNU4ATAC variants through various French and European networks and clinics, to refine the phenotypic spectrum of RNU4ATAC-opathies.

RESULTS: We enrolled 69 participants and identified 18 new pathogenic variants. We report a significant proportion of attenuated/atypical presentations, novel rare symptoms, and, unexpectedly, a broad spectrum of autoimmune/inflammatory manifestations, affecting nearly half of the participants. Integrating our data with the 109 published cases, we propose a novel classification based on the main manifestations, immunodeficiency and microcephalic primordial dwarfism. Using computer-assisted facial analysis, we also demonstrated the existence of a specific dysmorphic pattern in RNU4ATAC-opathies, distinct between some sub-syndromes.

CONCLUSION: We present a large cohort of individuals with RNU4ATAC-opathies and expand the phenotypic spectrum to pauci-symptomatic forms, indicating that these diseases are likely to remain underdiagnosed.

PMID:42322192 | DOI:10.1016/j.gim.2026.102632

Genet Med. 2026 Jun 19:102637. doi: 10.1016/j.gim.2026.102637. Online ahead of print.

ABSTRACT

PURPOSE: SET is a member of the inhibitor of histone acetyltransferases (INHAT) complex, involved in transcriptional silencing and gene regulation. Pathogenic variants in SET are postulated to cause neurodevelopmental disorder (NDD) phenotypes, but as only few individuals are described, detailed clinical information is scarce. Hence, currently counseling on phenotype and prognosis of this condition remains challenging.

METHODS: Here we describe the clinical phenotype and mutational spectrum of 23 unreported individuals harboring (likely) pathogenic variants in SET.

RESULTS: Phenotypes include global developmental delay with often pronounced hypotonia, delayed motor development and speech and language delay, ultimately evolving into (mild) intellectual disability. Comorbidities include behavioral concerns, sleeping disturbance and variable unspecific ocular problems. Next generation computer-assisted phenotyping using GestaltMatcher showed limited overlapping facial features between affected individuals and differences compared to disorders caused by related chromatin modifying genes. In addition, we generated a DNA methylation signature, able to distinguish individuals carrying pathogenic variants in SET from individuals with other NDDs and healthy controls. We used this DNA methylation signature to assess pathogenicity of two variants of uncertain significance in SET found in two additional individuals.

CONCLUSION: Together, this expands the knowledge on the SET-related disorder and provides novel approaches for its diagnosis.

PMID:42322191 | DOI:10.1016/j.gim.2026.102637

ScientificWorldJournal. 2026;2026(1):e3077222. doi: 10.1155/tswj/3077222.

ABSTRACT

BACKGROUND: Diabetic foot ulcers are a major complication of diabetes and contribute significantly to morbidity and healthcare burden in India. Physiotherapists play a vital role in prevention and management; however, their knowledge, attitude, and clinical practices in the Indian context remain unexplored.

OBJECTIVE: The study is aimed at assessing the knowledge, attitudes, and practices (KAP) of physiotherapists practicing across India regarding diabetic foot care through a national online cross-sectional survey.

METHOD: A cross-sectional national online survey was conducted from January 2024 to March 2025 among physiotherapists practicing across India. A total of 249 participants were included using a convenience sampling technique. Data were collected using a self-developed, content-validated questionnaire consisting of 20 questions across knowledge, attitude, and clinical practice domains. Descriptive statistical analysis was performed using Jamovi (2.6.23).

RESULTS: A total of 249 respondents from 28 Indian states were included. While 94.8% acknowledged their role in diabetic care, only 41% had received formal training in diabetic foot management. Although most participants identified clinical signs of complications, inconsistencies were observed in interpreting ABI and HbA1c values. Although 98.8% reported providing patient education practices, only 47.4% performed routine foot assessments. Greater clinical experience was associated with better application of knowledge in practice.

CONCLUSION: Indian physiotherapists demonstrate positive attitudes toward diabetic foot care; however, gaps remain in formal training and consistent clinical practice persist. Strengthening structured education and developing standardized clinical guidelines are essential to improve practice.

PMID:42322180 | DOI:10.1155/tswj/3077222

Histopathology. 2026 Jun 20. doi: 10.1111/his.70205. Online ahead of print.

ABSTRACT

AIMS: Appendiceal goblet cell adenocarcinoma (GCA) is an uncommon malignancy that has been described under various names and grading schemes. The 5th Edition of the World Health Organization (WHO) Classification of Digestive System Tumours provides a three-tiered system for grading these neoplasms, but the reproducibility of this classification scheme has not been studied.

METHODS AND RESULTS: We scanned 58 H&E-stained slides from 20 GCA and circulated the whole-slide images among seven pathologists with interest in appendiceal pathology. They evaluated each slide for the presence of 15 histological patterns defined by the WHO as criteria for low-grade (n = 5) and high-grade (n = 10) GCA. Cases were also evaluated for the presence of extracellular mucin. Participants also reported the percentage of high-grade features in each whole slide image and each case. Interobserver variability was assessed statistically. All seven observers agreed on the WHO grade for four of the 20 cases (20%; one grade 1, three grade 3). Using Fleiss’s kappa statistic, overall agreement for cases was fair at 0.29 (95% confidence interval [CI]: 0.14-0.44), and pairwise agreement between observers ranged from 0.00 to 0.82 (median = 0.13). Gwet’s agreement coefficient ranged from 0.10 to 0.87 (median = 0.28), while overall agreement was 0.36 (95% CI: 0.17-0.54). There was significant variability with respect to assessing the presence of individual features. The best agreement was seen for extracellular mucin (neutral feature, κ = 0.43) and tumour sheets (high-grade feature, κ = 0.41), whereas the worst agreement was seen for mild architectural disarray/tubular fusion (low-grade feature, κ = 0.05) and necrosis (high-grade feature, κ = 0.07).

CONCLUSIONS: We conclude that interobserver agreement for grading GCA using the three-tiered WHO 5th Edition classification system is fair at best. A validated two-tiered system (i.e. low- versus high-grade) may be more reproducible.

PMID:42322148 | DOI:10.1111/his.70205

Phys Occup Ther Pediatr. 2026 Jun 20:1-14. doi: 10.1080/01942638.2026.2689068. Online ahead of print.

ABSTRACT

AIMS: To evaluate cognitive and executive function (EF) in children with obstetric brachial plexus injury (OBPI), and the potential effects of injury severity and surgical intervention.

METHODS: Fifty-two children aged 6-12 years were assessed: 30 with OBPI (Type IIa: n = 10, Type IIb: n = 11, Type III-IV: n = 9) and 22 children with typical development. Cognitive function was measured using the Dynamic Occupational Therapy Cognitive Assessment for Children (DOTCA-Ch), and EF was assessed via parent-reported Childhood Executive Functioning Inventory (CHEXI). Non-parametric tests and subgroup analyses were conducted, with false discovery rate (FDR) correction applied for multiple comparisons.

RESULTS: Children with OBPI scored significantly lower on total and domain-specific DOTCA-Ch measures (median [IQR]: 85 [72-95] vs. 125 [115-135]; q = 0.002), with large effect sizes (Cliff’s δ = -0.82 to -0.90). No significant differences were found in CHEXI EF composites. Subgroup analyses showed no statistically significant effects of surgery or Narakas classification, although trends indicated potentially poorer cognitive outcomes in children with Narakas type III-IV.

CONCLUSION: Children with OBPI had lower cognitive function than children with typical development but there was no difference in EF. Findings support integrating cognitive assessments into management of children with OBPI.

PMID:42322142 | DOI:10.1080/01942638.2026.2689068

Lymphat Res Biol. 2026 Jun 20:15578585261461974. doi: 10.1177/15578585261461974. Online ahead of print.

ABSTRACT

PURPOSE: In times when health and physical activity are gaining in value, the search for effective methods to support fitness and improve quality of life is becoming a priority. One of the therapies that is gaining increasing popularity is pressotherapy, which supports the regeneration of the body on many levels.

METHODS: The study was conducted on a group of 15 healthy, young women. The participants underwent 10 pneumatic compression therapy treatments using the CarePump Expert8 device. The participants were examined 4 times: a week before the first treatment, immediately before the first treatment, after the 10th treatment and a week after the 10th treatment.

RESULTS: Statistical analysis of mean changes in the range of motion values showed significant decrease in: right (p < 0.05) and left (p < 0.05) hip joint extension; right (p < 0.05) hip joint horizontal abduction; horizontal adduction of the right (p < 0.05) and left (p < 0.05) hip joint; dorsiflexion of the right (p < 0.05) and left (p < 0.05) ankle joint, and also an increase in: right (p < 0.05) and left (p < 0.05) hip external rotation. Statistical analysis of changes in mean values of circumferences showed significant decrease at all tested levels: P1 right (p < 0.05) and left (p < 0.05); U1 right (p < 0.05) and left (p < 0.05); U2 right (p < 0.05) and left (p < 0.05); K right (p < 0.05) and left (p < 0.05); G1 right (p < 0.05); and left (p < 0.05); G2 right (p < 0.05) and left (p < 0.05).

CONCLUSIONS: A series of pressotherapy sessions did not improve lower limb range of motion or body composition indices; however, it did reduce circumferences at all levels of the lower limbs. Long-term use of pressotherapy can help maintain healthy fluid levels, improve circulation, and improve overall physical fitness.

PMID:42322135 | DOI:10.1177/15578585261461974

Am J Phys Med Rehabil. 2026 Jun 22. doi: 10.1097/PHM.0000000000003068. Online ahead of print.

ABSTRACT

Clinically meaningful outcomes require more than statistical significance; they must also represent an actual benefit to patients. The minimum clinically important difference (MCID) is the smallest change in a patient-reported outcome measure (PROM) that is clinically significant to the patient. Despite the growing use of PROMs in clinical research, considerable variability exists in how MCID is defined, calculated, and interpreted across populations and clinical contexts. The objective of this review is to provide a comprehensive summary of the various methods for estimating and interpreting MCID, including distribution-based, anchor-based, and Delphi approaches, and to discuss their relationship with statistical significance in clinical practice. A literature search was conducted using Web of Science, MEDLINE, Embase, PubMed, and Google Scholar. MCID values may vary depending on the patient population, clinical context, and the PROM administered. Each calculation methodology has its strengths and limitations in evaluating clinically meaningful change from baseline to post-treatment. It is recommended to report both a statistically significant difference, defined as P < 0.05, or equivalently a 95% confidence interval (CI) that excludes the null value (i.e., does not include 0 for mean differences or 1 for odds ratios), and a clinically meaningful difference, defined as an effect size meeting or exceeding the established MCID for the outcome measure. Reporting the effect estimate alongside its 95% CI is encouraged as the primary approach, as this conveys both the magnitude and precision of the finding.

PMID:42322131 | DOI:10.1097/PHM.0000000000003068

Clin Adv Periodontics. 2026 Jun 20. doi: 10.1002/cap.70075. Online ahead of print.

ABSTRACT

BACKGROUND: Soft tissue grafts are commonly used in periodontal surgery around teeth and implants. However, few studies have examined donor-site pain through patient-reported outcomes following soft tissue grafting. This study aimed to minimize donor-site pain during autologous gingival grafting using a three-dimensionally (3D)-printed stent and evaluate its effectiveness from a patient-centered perspective.

METHODS: In this randomized controlled trial, 32 patients requiring autogenous gingival grafts were equally allocated to the control group (Omnivac stent) or the test group (3D-printed stent). Patient-reported outcomes were assessed using a visual analog scale (VAS) and the Oral Health Impact Profile-14 (OHIP-14) questionnaire on the day of surgery and at 1, 7, and 14 days postoperatively.

RESULTS: Data from 16 control and 14 test patients were analyzed (two patients were lost to follow-up). The test group reported significantly lower VAS scores than the control group. Despite a lack of statistically significant temporal differences, marked reduction was observed on the day of surgery and on postoperative day 7. OHIP-14 scores were significantly lower in the test group than in the control group across all time points. Analysis of the individual OHIP-14 items at different intervals revealed significant reductions in discomfort-specifically in pronunciation, taste, mastication, and daily activities-when using 3D-printed stents.

CONCLUSIONS: This study applied 3D-printed stents to reduce donor-site discomfort after autogenous soft tissue grafting and evaluated their effectiveness using patient-reported outcomes. Although 3D-printed stents may not directly reduce postoperative pain, they help alleviate discomfort during routine oral functions and daily activities.

KEY POINTS: This study focuses on the free gingival graft, one of the most frequently employed soft tissue grafts in periodontal practice. While autogenous gingival grafting on the palatal side is currently considered the gold standard, it causes additional pain and discomfort in patients. This study demonstrates that three-dimensional technology can be used to improve stent design to reduce patient pain and discomfort.

PLAIN LANGUAGE SUMMARY: This randomized controlled trial demonstrates that compared with a conventional stent, a customized 3D-printed palatal stent significantly improves patient-reported comfort and oral function after autologous gingival grafting, thereby enhancing postoperative quality of life.

PMID:42322120 | DOI:10.1002/cap.70075

Ann Med. 2026 Dec;58(1):2534083. doi: 10.1080/07853890.2025.2534083. Epub 2026 Jun 19.

ABSTRACT

OBJECTIVES: This meta-analysis aimed to evaluate the association between endometriosis (EM) and cardiovascular disease (CVD) risk by synthesizing evidence from large-scale cohort studies, with emphasis on subtype-specific risks and geographic disparities.

METHODS: We systematically searched PubMed, Embase, and Cochrane Library for cohort studies published until December 2024. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses stratified CVD subtypes (e.g. ischemic heart disease, atrial fibrillation), continents, and country development levels. Heterogeneity and publication bias were assessed via I² statistics, sensitivity analyses, and Egger’s test.

RESULTS: Eleven cohort studies (n = 3,100,610 participants) were included. EM was associated with a 22% increased risk of all-cause CVD (HR = 1.22; 95% CI: 1.08-1.38; I² = 94.6%). Subgroup analyses revealed elevated risks for myocardial infarction (HR = 1.29; 95% CI: 1.10-1.50), coronary artery disease (HR = 1.47; 95% CI: 1.29-1.67), and cerebrovascular events (HR = 1.18; 95% CI: 1.12-1.25), but not heart failure. Geographic disparities were significant, with higher CVD risks in Asian (HR = 1.36; 95% CI: 1.25-1.48) and North American cohorts (HR = 1.37; 95% CI: 1.16-1.61) compared to European populations (HR = 0.93; 95% CI: 0.64-1.34).

CONCLUSIONS: EM is independently associated with an elevated risk of CVD, particularly for coronary artery disease and myocardial infarction. These findings underscore the need for targeted cardiovascular monitoring in EM patients, particularly in high-risk populations.

PMID:42322096 | DOI:10.1080/07853890.2025.2534083

Eur J Haematol. 2026 Jun 19. doi: 10.1111/ejh.70247. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of the complement C3 inhibitor pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria (PNH).

METHODS: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies reporting pegcetacoplan use in PNH. Outcomes included transfusion-requirement, hemoglobin normalization, mean hemoglobin levels, lactate dehydrogenase normalization, reticulocyte count normalization, and safety endpoints. Pooled proportions with 95% confidence intervals were calculated using random-effects models, and heterogeneity was assessed using the I² statistic.

RESULTS: Five studies comprising 271 patients were included. Transfusion avoidance was observed in 80.6% of patients, with a pooled transfusion-requirement rate of 19.4%. LDH normalization occurred in 68.5% of patients (I² = 0%). Hemoglobin normalization was observed in 42.9%, while reticulocyte count normalization reached 66%. Any-grade adverse events occurred in 83.5% of patients, most commonly pyrexia, headache, and dizziness. Serious adverse events occurred in 16.6%, decreasing to 12% after sensitivity analysis. Breakthrough hemolysis was reported in 14.8%, and infections in 17%.

CONCLUSION: Pegcetacoplan demonstrates consistent efficacy signals across key hematologic endpoints and an acceptable safety profile, supporting its potential role as an important therapeutic option, particularly in patients with persistent extravascular hemolysis despite C5 inhibition.

PMID:42322093 | DOI:10.1111/ejh.70247