bluuebunny/crossref_metadata_2025 huggingface dataset:
Informal care and cognitive frailty among Chinese older adults: the mediating role of social participation
Authors: Gao Tianyu , Zhao Dan , Chai Shujun , Liu Yang , Sun Yihong , Zhang Yuxun , Lin Zihan , Zhou Jie , Zhou Chengchao
Published: October 2024

Background and Objectives: With the intensification of ageing, cognitive frailty has become a major public health issue. The underlying mechanisms of the association between informal care and cognitive frailty were poorly understood. This study aimed to examine the mediating effect of social participation in the relationship between informal care and cognitive frailty among Chinese older adults.
Research Design and Methods: This research included 2,066 participants aged 60 and above from the China Longitudinal Study of Health and Retirement (CHARLS). We conducted the logistic regression model and Karlson-Holm-Breen(KHB) analyses to test the mediating role of social participation in the relationship between informal care and cognitive frailty.
Results: After adjusting the confounders, three dimensions ofinformal care were negatively associated with cognitive frailty (financial support: b = -0.110, P = 0.025; emotional support: b = -0.145, P = 0.037; life care:b = -0.304, P = 0.007). Social participation mediated the association between financial support and cognitive frailty (P = 0.008), as well as life care and cognitive frailty (P = 0.022). However, the mediating effect of social participation on the association between emotional support and cognitive frailty was insignificant (P = 0.660).
Discussion and Implications: Cognitive frailty was associated with informal care among Chinese older adults. Social participation mediated the association between financial support and cognitive frailty, as well as life care and cognitive frailty. More attention should be devoted to promoting social participation among Chinese older adults with cognitive frailty, especially those who receive life care and financial support.
Association between biological aging and the risk of stroke: Results from the National Health and Nutrition Examination Survey and Mendelian randomization analysis
Authors: Zhang Zhaoqi , Zhao Xingru , Yang Kai , Gao Shang , Zhang Jie , Li Xin , Liu Wei
Published: October 2024

Introduction:
Stroke is an acute cerebrovascular disease that seriously affects lifespan, and aging is generally considered an important risk factor for stroke. This study aimed to explore the association between biological aging and stroke risk using well-validated measures of aging.
Methods
We employed the methods of Klemera-Doubal (KDMAge) and phenotypic age (PhenoAge) as alternative measures of biological aging in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. In order to analyze the data, we employed logistic regression, trend p-value, restricted cubic spline (RCS) analysis, and subgroup analysis. Furthermore, a bidirectional two-sample Mendelian randomization (MR) analysis was conducted to assess the potential causal impact of biological aging (including intrinsic age acceleration, telomere length, facial aging, and frailty index) on stroke and stroke subtypes.
Results
A cross-sectional analysis of 34,856 participants revealed that higher biological age or biological age acceleration was associated with an increased risk of stroke. Furthermore, multivariate logistic regression analysis performed in 5 models revealed a statistically significant association between biological age or biological age acceleration and stroke risk. RCS analysis showed that there is a nonlinear relationship between KDMAge and KDMAge acceleration and stroke. Subgroup analysis revealed a moderating effect of alcohol consumption on the association between KDMAge acceleration and stroke risk. Finally, MR analysis revealed that the frailty index was associated with an increased risk of stroke (OR: 1.57, 95% CI: 1.36–1.83, p < 0.001). In contrast, reverse MR analysis revealed that stroke was associated with PhenoAge accelerated (OR: 1.54, 95% CI:1.12–2.12,p = 0.008), frailty index (OR:1.11,95% CI:1.05–1.17, p < 0.001) and facial aging (OR:1.02, 95% CI:1.01–1.03, p = 0.001). These findings provide evidence for a potential causal relationship between biological aging and stroke risk.
Conclusion
There is a significant association between biological aging and stroke. It is possible that biological aging may be a risk factor for stroke, and that stroke may further accelerate the process of biological aging. Consequently, it is of paramount importance to identify the acceleration of biological aging through biological aging measures with the objective of reducing the risk of stroke and the occurrence of adverse events.
Proactive symptom monitoring to initiate timely palliative care for patients with advanced cancer: a randomized controlled trial
Authors: YANG Grace Meijuan , KE Yu , NG Xin Hui , NEO Patricia Soek Hui , CHEUNG Yin Bun
Published: October 2024

Purpose
To deliver timely palliative care in response to supportive and palliative care needs as they arise, we developed a model called ‘Supportive and Palliative care Review Kit in Locations Everywhere’ (SPARKLE), which comprises regular remote symptom monitoring using the Integrated Palliative care Outcome Scale (IPOS); early identification and prompt treatment of palliative care symptoms and concerns identified; referral to specialist palliative care if follow-up is required.
Methods
A prospective randomized controlled trial of SPARKLE versus usual care was conducted among patients with advanced cancers. The primary endpoint was Functional Assessment of Cancer Therapy – General (FACT-G) scores at 16 weeks post randomization.
Results
A total of 239 patients were randomized – 119 patients to usual care and 120 patients to SPARKLE intervention. There was no significant difference in total FACT-G score (baseline-adjusted difference 0.8, 95% CI -3.5 to 5.1, p = 0.73). Physical wellbeing was better in the SPARKLE intervention group compared to the usual care group (baseline-adjusted difference 1.9, 95%CI 0.4 to 3.4, p = 0.01). There were no significant differences in the other domain scores. There were no differences in palliative care referrals, occurrence of emergency department visits and/or hospital admissions.
Conclusion
Although there was no significant difference in overall quality of life, better physical symptom control could have been achieved through proactive identification and treatment of symptoms and concerns by the SPARKLE nurse. Further studies are warranted to evaluate how various components of palliative care service models impact clinical outcomes.
Trial registration
ClinicalTrials.gov identifier: NCT04242251
Prognostic value of MR visibility/invisibility in men on Active Surveillance
Authors: Klotz Laurence , Loblaw Andrew , Zhang Liying , Mamedov Alexandre , Vesprini Danny
Published: October 2024

We sought to determine, in a prospective long term cohort, the prognostic value of negative MR imaging with respect to upgrading and need for intervention in men on AS.
Method: A long term prospective single centre study of men on Active surveillance with MR imaging. Primary outcome was upgrading on biopsy and rate of intervention. After incorporation of MRI into the AS protocol in 2013, men with negative imaging underwent systematic biopsy only for cause.
Results: 530 AS patients had one or more MRI, with median follow up of 8.5 years. At baseline, 39 patients (7.4%) had negative MRIs 161 (30%) equivocal,and 330 (62%) had a positive MRI. 229 patients were upgraded; 5% with invisible lesions, 34% with PiRADS 3, and 52% with PiRADS 4-5. 229 (43%) of the 530 men were eventually treated. No patient with a negative PiRADS was treated, vs 36% with PiRADS 3 and 52% with PiRADS 4-5 (p<.001).
In 331 men with serial MRIs, upgrading occurred in 46% of men with stable or improved MRI, and 57% in those with MRI progression. In the 70 patients whose MRI improved from PiRADS 4-5 to 3, 46% were upgraded. No patients who transitioned from PiRADS 3-5 to 1-2 were upgraded. Time to grade progression was highly inversely correlated with PIRADS score.
Conclusion: MRI invisible cancers demonstrated dramatically reduced rates of progression and no patient required intervention. Despite the absence of routine biopsies in the MR negative group, none of these patients progressed over time to GG ≥ 3 or metastatic disease. This suggests that, in men on active surveillance, image guided management, restricting biopsies to targeted biopsies of regions of interest, is sufficient to identify clinically significant cancers.
Do CRP Gene Variants and Smoking Elevate Recurrent Stroke Risk in Minor Ischemic Stroke Patients?
Authors: Li Xiaofeng , Song Shina , Jia Wenhui , Xie Lihua , Fan Meilin , Li Changxin
Published: October 2024

Background
Minor ischemic strokes, though initially presenting with limited symptoms, carry a significant risk of recurrence, potentially leading to severe disability. However, the association of CRP gene variations in predicting the risk for recurrent minor stroke, especially how genetic susceptibility interacts with poor health habits like smoking, still needs to be established. This study investigates the relationships of single-nucleotide polymorphisms (SNPs) in CRP gene with minor stroke recurrence. Furthermore, this research proceeds to explore the potential interactions between these genetic variants and smoking status.
Methods
A total of 2,032 first-time minor stroke patients were retrospectively recruited from January 2019 to December 2022 in Linfen People's Hospital. Genomic DNA was extracted for genotyping four SNPs of the CRP gene: rs1130864, rs1800947, rs2808632, and rs3093059. We scrutinized the association of these SNPs with the risk of stroke recurrence in an additive, dominant, and recessive genetic model. To further explore this complicated interaction of the CRP gene SNPs with the status of smoking, the tool of Generalized Multifactor Dimensionality Reduction (GMDR), was employed. Besides, multivariate logistic regression was used to estimate the strength of these associations with the risk of recurrence. The patients were followed by a team of three trained rehabilitators, making evaluations every three months for one year, in a very thorough follow-up.
Results
Our study recruited 260 patients who suffered recurrent minor strokes and 264 age- and sex-matched controls without recurrence. The A allele of rs2808632 (P = 0.002) and C allele of rs3093059 (P = 0.009) were found to be significantly associated with high risk of stroke recurrence by analysis. Those patients with the combined genotypes rs2808632 CA + AA and rs3093059 TC + CC revealed 2.325 times more risk for recurrence when compared to those with the genotypes rs2808632 CC and rs3093059 TT (P = 0.002). Furthermore, in the rs3093059 TC + CC genotypes versus the TT genotype among the smokers, an associated 3.467-fold increased risk for recurrence had been confirmed.
Conclusion
Our results confirmed that rs2808632 and rs3093059 together are pivotal factors in contributing to heightened minor stroke recurrence. Besides, this significantly affects the interaction between rs3093059 SNP and smoking status.
Mild Neurodevelopmental Disorder Due to SHMT2 Mutations: Expanding the Phenotypic Spectrum
Authors: Pan Hu , He Mei , Luo Xuan , Hu Juanli , Mao Xiao , Cheng Yong , Liu Zhen
Published: October 2024

Biallelic mutations in SHMT2 cause neurodevelopmental disorders with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB; OMIM: 619121). This recently described metabolic disorder are characterized by severe intellectual disability, microcephaly, spastic paraplegia, peripheral neuropathy, corpus callosum dysgenesis, facial and limb deformities, and progressive hypertrophic cardiomyopathy. Herein we describe the clinical characteristics of a patient with novel compound heterozygous SHMT2 missense variants (c. 1274G > A: p.R425Q and c.1042C > T: p.R348W), presenting with mild intellectual disability, corpus callosum dysgenesis, and speech delay. Different from previous cases, our patient represents the mildest phenotype reported to date, and expand the phenotypic spectrum of disease associated with SHMT2 mutation.
Epidemiology and Genetic Characterization of Rabies Viruses in Middle of China
Authors: Yun Song , Xue Luo , Yifei Nie , Bicong Wu , Hongxia Ma , Jingjing Pan , Haifeng Wang , Ying Ye , Xueyong Huang , Wanshen Guo
Published: October 2024

Background
To analyze the epidemiological characteristics of human rabies in Henan Province and perform a genetic characterization of the rabies virus (RABV).
Methods
The rabies case data were retrieved from the National Infectious Disease Reporting Information Management System and individual case investigation forms. Saliva, cerebrospinal fluid and serum samples from rabies patients were collected and tested via real-time PCR. Positive samples were subjected to sequencing of the RABV N gene, and the sequences were compared with reference sequences in GenBank for homology and phylogenetic analysis.
Results
Among the five rabies cases (cases 1–5) examined, two were associated with bites from domestic dogs and were classified as level III exposure. The exposure source and level for the remaining three cases were unknown. None of the patients had received vaccination or passive immunization. Real-time PCR tests revealed that saliva samples had the highest positivity rate (87.5%), whereas CSF and serum samples tested negative for viral RNA. The N gene sequences from the four rabies cases (cases 1–4) were identified as belonging to the China I strain, a dominant rabies virus strain in China, with nucleotide homology ranging from 99.26%-99.85% and amino acid homology of 100%. The major functional and antigenic sites of the encoded protein are highly conserved.
Conclusion
Rabies continue to circulate in Henan Province. However, the evolutionary diversity and genetic stability of circulating strains of the rabies virus are limited.
Comparison of 2D, 2.5D, and 3D segmentation networks for mandibular canals in CBCT images: A study on public and external datasets
Authors: Yang Su , Jeong Jong Soo , Song Dahyun , Han Ji Yong , Lim Sang-Heon , Kim SuJeong , Yoo Ji-Yong , Kim Jun-Min , Kim Jo-Eun , Huh Kyung-Hoe , Lee Sam-Sun , Heo Min-Suk , Yi Won-Jin
Published: October 2024

The purpose of this study was to compare the performances of 2D, 2.5D, and 3D CNN-based segmentation networks, along with a 3D vision transformer-based segmentation network, for segmenting mandibular canals (MCs) on the public and external CBCT datasets under the same GPU memory capacity. We also performed ablation studies for an image-cropping (IC) technique and segmentation loss functions. 3D-UNet showed the highest segmentation performance for the MC than those of 2D and 2.5D segmentation networks on public test datasets, achieving 0.569 ± 0.107, 0.719 ± 0.092, 0.664 ± 0.131, and 0.812 ± 0.095 in terms of JI, DSC, PR, and RC, respectively. On the external test dataset, 3D-UNet achieved 0.564 ± 0.092, 0.716 ± 0.081, 0.812 ± 0.087, and 0.652 ± 0.103 in terms of JI, DSC, PR, and RC, respectively. The IC technique and multi-planar Dice loss improved the boundary details and structural connectivity of the MC from the mental foramen to the mandibular foramen. The 3D-UNet demonstrated superior segmentation performance for the MC by learning 3D volumetric context information for the entire MC in the CBCT volume.
The relationship between the number of foods suitable for intake and comprehensively assessed oral function: A cross-sectional study
Authors: Futatsuya Ryota , Hama Yohei , Okada Mitsuzumi , Matsuzaki Mayuko , Xiong Linjing , Yamaguchi Kohei , Noritake Kanako , Sasaki Yoshiyuki , Kanazawa Manabu
Published: October 2024

Background
With a globally aging population, the relationship between oral function and the risk of long-term care is attracting attention. One method for the subjective assessment of oral function is the use of a questionnaire on the number of foods suitable for intake. Although it is possible that objective oral functions, such as tongue pressure and maximum occlusal force, are associated with the number of foods suitable for intake, this relationship has yet to be investigated. This study aimed to clarify the association between overall oral function and the number of foods suitable for intake.
Methods
Patients aged 65 years or older were recruited from an outpatient dental clinic at Tokyo Medical and Dental University. The number of foods that they could consume was assessed using the food acceptance score. Seven oral function parameters, as defined by the Japanese Society of Gerodontology, were also measured. Age, sex, the number of functional teeth, geriatric depression, cognitive function, and oral health-related quality of life were assessed. Variables for which normality was rejected were transformed into tertiles. Multiple regression analysis was performed with the food acceptance score as the objective variable, and each oral function and other items as explanatory variables.
Results
This study included 201 participants (87 men, 114 women). Multiple regression analysis revealed that the number of functional teeth, geriatric depression, oral-related quality of life, masticatory function, tongue pressure, and swallowing function were significantly associated with food acceptance scores.
Conclusions
This study showed that the number of foods suitable for intake was independently associated with tongue pressure, masticatory function, swallowing function, the number of functional teeth, geriatric depression, and oral-related quality of life.
Epidemiology of invasive pneumococcal disease in western Sweden during the first 11 years after the introduction of general childhood pneumococcal vaccination
Authors: Härnqvist Tor , Bergman Karin , Backhaus Erik , Dahl Mats , Kolberg Helena , Turesson Caroline Ström , Olander Malin , Nilsson Staffan , Andersson Rune , Skovbjerg Susann , Karlsson Johanna
Published: October 2024

Background
Invasive pneumococcal disease (IPD) still causes significant morbidity and mortality. In this study, we describe incidence, risk factors, manifestations, and outcome of IPD in Southwest Sweden during the first 11 years following the introduction of pneumococcal conjugate vaccines (PCV) in the childhood vaccination program in 2009.
Methods
Clinical data from 2,288 consecutive episodes of IPD in Region Västra Götaland, Sweden, during 2009–2019 were retrospectively collected from medical records. Incidence rates were calculated using population data from the same period. The results were compared to data from three previous studies from the same geographical area with a total follow-up of 56 years.
Results
The incidence of all IPD episodes in 2009–2019 was 12.8/100,000/year. In children < 2 years, this declined from 22.5 in 1996–2008 to 10.7 per 100,000 in 2009–2019, while only a modest reduction was observed in adults. A very high incidence of IPD was seen in patients with multiple myeloma (1,497/100,000) and chronic lymphocytic leukemia (505/100,000). Meningitis occurred in 26% of the IPD episodes in children < 2 years compared to 4.3% in the age group ≥ 65 years (12/46 versus 60/1,403; p < 0.001). An opposing trend was found for pneumonia, which accounted for 22% of the IPD episodes in children < 2 years compared to 77% among the elderly (10/46 vs. 1,085/1,403; p < 0.001). In 604 IPD episodes (26.4%) one or more complications were observed. The case fatality rate increased from 9.9% pre-PCV to 12.9% in the post-PCV period. This was highest among patients with detected bacteremia but with no other clinical manifestations, those admitted to intensive care, and those with hospital-acquired IPD.
Conclusions
A substantial decrease in IPD incidence was seen in infants and young children but not in the elderly after introduction of PCV in the general childhood vaccination program. The higher IPD mortality post-PCV could be explained by higher age and increased comorbidity among the patients. Patients with hematological malignancies showed a very high risk for IPD.
Improving ROP Management: Insights from a Comparative Analysis of Screening and Treatment Modalities in a Tertiary Hospital, Pakistan
Authors: Moin Muhammad , Azam Aisha , Mian Lubna Siddique , Pal Ashal Kaiser , Kareem Rutaab , Us-Sehar Noor
Published: October 2024

BACKGROUND
The principal objective of our study is to evaluate the characteristics of babies with type 1 ROP, screening practices and treatment trends in a tertiary care centre in Pakistan.
METHODS
This prospective study at Mayo Hospital, Lahore (July 2022–July 2024), included 89 preterm infants with type 1 ROP, selected using non-probability sampling. Infants were categorized based on international (GA < 32weeks or BW < 1500g) and local screening criteria (GA < 35 weeks or BW < 2000g), and treatment outcomes were evaluated across three groups: Anti-VEGF, combination therapy (Anti-VEGF followed by laser), and laser therapy. Statistical analysis was performed using SPSS version 27.0, employing Chi-square and Fisher Exact test for categorical variables. Statistical significance was set at p < 0.05.
RESULTS
Out of 355 infants screened, 89 (25.1%) met the inclusion criteria for type 1 ROP. The cohort included 55 males (61.8%) and 34 females (38.2%), with a mean gestational age of 31.31 weeks and a mean birth weight of 1602.25 grams. Zone 1 ROP was found in 36% of cases, associated with lower birth weight (P = 0.029) and earlier gestational age (P = 0.037), while Zone 2 ROP, found in 64%, was linked to higher birth weight and later gestational age. Zone 1 infants were more likely to receive anti-VEGF or combination therapy, whereas Zone 2 infants predominantly received laser therapy (p < 0.000). Preterm infants (born before 32 weeks) mostly received Anti-VEGF or combination therapy, while those with higher birth weights primarily received laser therapy (p < 0.010). Among the treated babies, 63 (70.8%) met international screening criteria and were more likely to have Zone 1 ROP and receive Anti-VEGF or combination therapy. Conversely, 26 (29.2%) did not meet these criteria, had predominantly Zone 2 ROP and were more likely to receive laser therapy (p = 0.007).
CONCLUSION
International screening criteria effectively identify severe type 1 ROP cases, particularly Zone 1, which often require Anti-VEGF therapy. Local criteria capture additional cases, predominantly Zone 2, which are more likely to need laser treatment. These findings highlight the need for tailored screening and treatment approaches to improve ROP management and outcomes for preterm infants
Correlation of inflammation/immunity markers with postoperative urinary tract infections in elderly hip fracture patients
Authors: Liu Xiao-yang , Guo Si-qin , Chen Xu-ming , Zeng Wei-nan , Zhou Zong-ke
Published: October 2024

Background
This study aimed to investigate the association between inflammation/immune markers and the occurrence of postoperative urinary tract infections (UTIs) in elderly patients with hip fractures.
Methods
This study examined elderly patients who underwent hip surgery for hip fractures at our institution. Inflammation/immune markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were measured. Receiver operating characteristic (ROC) curves were used to identify optimal cutoff values for each marker. To control the potential confounding factors, multivariate logistic regression analysis and propensity score matching analysis were conducted, resulting in adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the association between each marker and UTIs.
Results
A total of 1,238 patients were included in this study, of whom 287 (23.18%) developed postoperative UTIs. Among elderly hip fracture patients, NLR demonstrated the highest predictive value for postoperative UTIs compared to PLR and SII (area under the curve [AUC] = 0.608, 95% CI: 0.571–0.645). High NLR (OR = 1.57, 95% CI: 1.16–2.13), high PLR (OR = 1.59, 95% CI: 1.16–2.19), and high SII (OR = 1.75, 95% CI: 1.29–2.37) were significantly associated with the incidence of postoperative UTIs using the best cutoff values. Additionally, a dose-effect relationship was observed for this association (P for trend < 0.05). These results remained significant even after propensity score matching.
Conclusions
Inflammatory/immune markers NLR, PLR, and SII exhibited independent associations with the development of postoperative UTIs in elderly hip fracture patients undergoing surgery. Furthermore, a dose-effect relationship was observed for this association.
The landscape of gain and loss of function mutations in melanoma
Authors: Auslander Noam , Tsingas Konstantinos , Thomas Monzy , Duong Bryant , Xiao Min , Wickramasinghe Jayamanna , Chen Yeqing , Reale McKenna , Thacker Gatha , Li Haiyin , Mou Haiwei , Salazar Eric , Villanueva Jessie , Xu Xiaowei , Flowers Ahron J. , Karakousis Giorgos , Miura John , Mitchell Tara , Amaravadi Ravi , Schuchter Lynn , Liu Shujing , Long Qi , Hoon David , Ramos Romela ,   Matias A Bustos4, Gershenwald Jeffrey , Simon Julie , Wargo Jennifer , Davies Michael , lu yiling , Mills Gordon , Cohen Sonia , Lawless Aleigha , Sharova Tatyana , Frederick Dennie , Flaherty Keith , Hacohen Nir , Boland Genevieve , Herlyn Meenhard
Published: October 2024

Melanoma is a common and aggressive cancer, with a rising incidence in most developed countries. Major discoveries in melanoma biology have been rapidly translated, allowing cures for some late-stage patients. Despite these advances, incomplete knowledge of genes and pathways that are gained or lost during melanogenesis prohibits cures for many patients. To identify gain-of-function and loss-of-function drivers of melanoma, we established a multi-omics cohort of melanoma patient-derived xenografts. By linking mutations with gene and protein expression, we characterize gain or loss-of-function of specific melanoma drivers in treatment refractory tumor models. We use multi-omics integration and structural-context representation to distinguish gain from loss of function variants, revealing new candidate melanoma genes and targets. This study provides a comprehensive resource of tumor models with the genetic, molecular and structural features of gain and loss of function melanoma drivers, allowing future development of better therapeutics for this devastating and heterogenous malignancy.
Clinical and molecular genetic analysis of a Chinese patient with Cockayne syndrome caused by ERCC8 gene synonymous variation and exon 1 deletion
Authors: Bie Xiaofan , Liu Lei , Liu Lingzhi , Zhang Zhenkun , Guo Mingwei , Xie Zhenhua , Zhang Yaodong , Su Jun , Li Dongxiao
Published: October 2024

Background
Cockayne Syndrome (CS) is a rare autosomal recessive genetic disease, mainly caused by ERCC8 and ERCC6 gene defect. However, many of its molecular characteristics remain unclear. In this study, molecular genetic analysis was performed on a patient to clarify her genetic etiology.
Results
A 7-year-old girl fever for 4 days and thrombocytopenia for half a day. Her main clinical manifestations included lethargy after infection, short stature, microcephaly, mental retardation, facial aging, skin photosensitivity. Laboratory tests indicated liver and kidney damage, thrombocytopenia, and brain MRI revealed progressive brain damage. Whole exome sequencing showed that the proband had a c.1041G > A (p. Gln347Gln) heterozygous synonymous variation and a suspected heterozygous deletion in exon 1 of ERCC8 gene. Sanger sequencing and Quantitative real-time PCR were respectively used to confirm inheritance from her phenotypically normal mother and father. Transcriptome sequencing showed a deletion of exon 10. According to the ACMG guidelines, the two variations were classified as pathogenic variants.
Conclusions
This study reported the rare case of CS caused by the c.1041G > A synonymous variation causing exon 10 deletion by affecting splicing and exon 1 deletion by preventing its allele from initiating transcription, expanding the variation spectrum of the ERCC8 gene. And remindering us that although synonymous variations are rare, they may affect splicing when they occur at the junction of exons and introns.
Large size of the Australian Indigenous population prior to its massive decline following European invasion
Authors: Williams Alan , Tobler Raymond , Griffiths Billy , Ulm Sean , Nitschke Matthew , Bird Michael , Ingrey Shane , Saltré Frédérik , Beller Kirsty , McNiven Ian , Pitt Nicholas , Russell Lynette , Wilson Christopher , Bradshaw Corey
Published: October 2024

Estimating the size of Indigenous populations in Australia prior to European colonial invasion is essential to truth-telling and reconciliation. Robust estimates of the population dynamics of pre-colonial Indigenous Australians are poor due to lethal diseases, frontier violence, and no systematic censuses. We review ethnographic observations, archaeological and genetic reconstructions, and modelled carrying capacity, to infer Indigenous population size prior to colonial invasion. This allows an estimate of the number of excess deaths in post-colonial times. Congruency of the modelled (not historical accounts) estimates suggests a bootstrapped pre-colonial median of 2.51 million, or 0.33 people km-2. For a median pre-colonial population of 2.51 million, ~ 32,500 excess deaths year-1 (2.39 million deaths in total) would have had to occur over the late 18th and early 19th Centuries from colonial invasion-related mortality. These findings highlight the major impacts of invasion experienced by Indigenous Australians, and demonstrate their survival, resilience, and recovery over the past 235 years.
Anti-Photoelectrochemical (a-PEC) Etching
Authors: Fang Nicholas , Peng Pan , Liu Xinqin , Yang Shuming , Zhou Renjie , Deng Hui , Gao Liang , Liu Shiyuan , Zhu Jinlong
Published: October 2024

For more than 60 years, it has been widely accepted that the irradiance of the incoming light plays the most critical role in the etching effect of the photoelectrochemical (PEC) etching process, which is built upon the underlying physics that photo-generated charge carriers catalyze the dissolution of n-type semiconductors. However, in this paper, we report an unprecedented physical phenomenon, i.e., the spatially distributed photons with a lateral gradient could drive the lateral distribution of carriers on the surface of semiconductors, which leads to the anti-etching phenomenon on the surface of semiconductor materials during PEC etching process. This discovery catalyzes a new type of rapid and large-scale 3D nanomanufacturing paradigm on semiconductor materials, which holds promise for significant applications in diverse fields such as microelectronics, nanophotonics, metamaterials, and biomedicine.
An assessment of climate change impacts on stream phosphorus using a climate model ensemble and Bayesian Belief Networks
Authors: Negri Camilla , Cowdery Elizabeth , Schurch Nicholas , Wade Andrew J. , Mellander Per-Erik , Glendell Miriam
Published: October 2024

Climate-induced changes in precipitation and river flows are expected to cause changes in river phosphorus loadings. The uncertainty associated with climate-induced changes to water quality is rarely represented in models. Bayesian Belief Networks (BBNs) are probabilistic graphical models incorporating uncertainty in their model parameters, making them ideal frameworks for communicating climate risk. This study presents a set of catchment-specific BBNs to simulate total reactive phosphorus (P) concentrations in four agricultural catchments under projected climate change. Six climate models (five models plus the ensemble mean) across two objective functions (NSE vs log NSE), two Representative Concentration Pathways (RCP 4.5 and 8.5), and three time periods (the 2020s, the 2040s, and the 2080s) were used to create discharge scenarios as model inputs. The simulated monthly mean P concentrations show no obvious trends over time or differences between the two RCP scenarios, with the model ensemble essentially replicating the results obtained for the baseline period. However, the P concentration distributions simulated using the outputs from the HadGEM2-ES model rather than the ensemble, showed differences from the baseline in drier months. A sensitivity analysis demonstrated that this difference occurred because the catchment-specific BBNs were sensitive to changes in the mean total monthly discharge which were captured in the HadGEM2-ES projections but not by the ensemble mean.
Global Estimation of River Bankfull Discharge Reveals Distinct Flood Recurrences Across Different Climate Zones
Authors: Liu Yinxue , Wortmann Michel , Hawker Laurence , Neal Jeffery , Yin Jiabo , Santos Marcus Suassuna , Anderson Bailey , Boothroyd Richard , Nicholas Andrew , Smith Gregory Sambrook , Ashworth Philp , Cloke Hannah , Gebrechorkos Solomon , Leyland Julian , Zhang Boen , Vahidi Ellie , Griffith Helen , Delorme Pauline , McLelland Stuart , Parsons Daniel , Darby Stephen , Slater Louise
Published: October 2024

The maximum amount of water rivers can transport before flooding is known as the bankfull discharge, an essential threshold for flood risk and biogeochemical cycles. Current Global Flood Models rely on an untested assumption of a spatially-invariant, 2-year bankfull recurrence. Here, based on observations and machine learning, we deliver the first global estimation of bankfull discharge in different climates along a new bifurcating river network at ~ 1 km spatial resolution. In contrast to the 2-year assumption, we find rivers flood more frequently in tropical and temperate regions (median return periods of 1.5 and 1.8 years; IQR 2.5 and 3.2y, respectively), and less frequently in cold and arid regions (2.8/4.3 years; IQR 4.8/6.0y). Relative to observations, the 2-year assumption overestimates bankfull discharge in the tropics (54%±78%, mean ± std) and underestimates it in arid regions (10%±51%). This new understanding will transform our ability to make accurate global flood predictions.
Evaluation of arthroscopic repair in recurrent shoulder dislocation
Authors: Vo Thanh Toan , Nguyen Thien Duc , Vo Toan Phuc
Published: October 2024

Objective: To evaluate the outcomes of arthroscopic repair for recurrent shoulder dislocation and to identify the risk factors for recurrence and complications.
Method: A retrospective study of 51 patients who underwent arthroscopic repair for recurrent shoulder dislocation at Thong Nhat Hospital, Ho Chi Minh City, Vietnam from June 2015 to June 2020. Preoperative and postoperative data were collected and analyzed, including the Instability Severity Index Score (ISIS), range of motion (ROM), functional scores, pain score, and radiographic findings.
Result: The mean follow-up period was 24 months. The mean preoperative ISIS score was 1.25. The mean postoperative ROM of flexion and abduction improved significantly from 80.1° (58°-105°) to 83.8° (78°-90°), respectively. The mean postoperative functional scores (Constant, UCLA, and Oxford) also improved significantly from 68.6 (59-79) to 86.4 (81-92). The mean postoperative pain score (VAS) decreased significantly from 1.3 (0-7) to 0.45 (0-3). There were no cases of postoperative redislocation. The most common complications were cartilage loss (7.8%) and osteoarthritis (3.9%). The failure rate of arthroscopic repair was 5.9%, which required revision surgery.
Conclusion: Arthroscopic repair for recurrent shoulder dislocation is a safe and effective treatment option with low recurrence rate, good functional outcomes, and few complications. However, longer follow-up and larger sample size are needed to confirm the long-term results and to identify the optimal candidates for this procedure.
Primary care clinical practice guidelines in Sudan: A qualitative survey exploring national stakeholders’ perspectives
Authors: Abdelgadir Hiba Salah , Bajouri Sahar , Abdelgadir Hind Salah
Published: October 2024

Introduction:
The health system in Sudan faces several challenges, including increasing numbers of patients, shortages of health supplies, and disparities in the distribution of health services. Guidelines implementation improves patients’ outcomes and ensures efficient use of the resources in such a resource-limited country. This paper explored the practice of family medicine at primary health care centers addressing the struggles that impede guideline implementation from the national stakeholders' perspectives.
Methods:
A qualitative facility-based survey conducted in the public referral primary health care centers in Khartoum and Gezira States of Sudan. The study population was composed of practicing family medicine doctors the medical directors in the referral PHC centers. All the focused group discussions and the interviews were audio-recorded. Recordings were transcribed verbatim, and the transcriptions were anonymized. Thematic content analysis was used to analyze the data.
Results:
Local Sudanese guidelines are lacking good publication and regular updating of the recommendations. Most of the surveyed doctors reported reduction of the training programs that are regulated and funded by the ministry of health due to the political and economic situations in Sudan. Barriers to guidelines implementation include limited health insurance coverage, patients’ factors, absence of regular training programs, lack of filing and referral system. Massive deterioration in the family medicine practice at Gezira state was observed due economic and some governmental issues.
Conclusion:
Successful development, adaptation, and implementation of the CPG depends on many factors, including adequate resources, quality assurance, widespread dissemination, appropriate monitoring and auditing for quality improvement. Efforts should be directed to encourage the development of local guidelines through a rigorous approach that involves a multidisciplinary team representing various stakeholders. The government represented by National Health Insurance Fund must expand the health insurance coverage and services. Contribution of the reestablishment of the electronic filing system and the telemedicine consultation in Gezira state and expand the program in Khartoum state and whole Sudan.
Molecular characterization of virulence genes in quorum sensing system of different pathogenic strains of Pseudomonas aeruginosa from neonates with pulmonary infections using PCR as efficient technique
Authors: Chaudhry Maham , Rehman Safia , Zahid Sehar , Ali Nazish Mazhar , Ruhi Nabila , Liaqat Iram , Riaz Samreen
Published: October 2024

Background: The expectation from the current research study was to genetically identify the virulence genes involved in quorum sensing (QS) in different strains of Pseudomonas aeruginosa, as the QS controls production of many virulence factors.
Objective: The intention of current research study was to isolate the pathogenic strains of P. aeruginosa from sputum samples of neonates and infants and their molecular characterization.
Methods: P. aeruginosawere obtained from Microbiology Laboratory, Department of Zoology, Government College University Lahore were grown on selective media. Biochemical and molecular characterization was done. Molecular characterization was done by specific primers of quorum sensing virulent genes. Amplified genes were sequenced, and accession numbers were obtained from the NCBI site. Genes lasR, lasI, rhlR, and rhlI were identified in P. aeruginosa strains (ss5, ss6, and ss11).
Results: Current study revealed that these virulence genes are the main contributors of resistance of P. aeruginosa strains against different antibacterial agents.
Conclusion: P. aeruginosa is a Gram-negative bacterium with diverse metabolic capacity to regulate survival under many different conditions and can be highly resistant to antibiotics, facilitating its spread in diverse habitats, particularly in hospitals. These virulent genes contribute to the overall pathogenic potential of P. aeruginosa that facilitates its ability to cause disease.
WITHDRAWN: Excess Mortality in Alzheimer’s Patients on Anti-Aβ Monoclonal Antibodies
Authors: Dwivedi Alok K , Abanto Jesus , Schneider Lon S. , Herrup Karl , Schrag Matthew , Widera Eric , Mahajan Abhimanyu , Howard Robert , Espay Alberto J.
Published: October 2024

Introduction
It is unclear how the reported deaths of Alzheimer’s disease (AD) patients treated with the monoclonal antibodies lecanemab and aducanumab compare with background mortality rates.
Methods
Using post-marketing safety data from the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we assessed whether the fatalities associated with the real-world use of these drugs exceed the expected mortality rates in both clinical trials and the general AD population for the age range of deaths in FAERS (75-84 years), with a background mortality rate of 229.3 deaths per 100,000.
Results
FAERS recorded 25 deaths with lecanemab and 27 with aducanumab. Without available data on the exact number of patients treated, we assumed a range of 2,000 to 10,000 patients. The mortality rate was higher for lecanemab (RR = 2.6; 95% CI: 1.4-3.8) and aducanumab (RR = 3.9; 95% CI: 1.4-6.5) compared to the background mortality rate and the pivotal trials for lecanemab (RR = 1.87; 95% CI: 1.1-2.6) and aducanumab (RR = 2.7; 95% CI: 1.7-3.7). This corresponds to 21 excess deaths for lecanemab and 41 excess deaths for aducanumab per 10,000 patients treated.
Conclusion
These findings suggest a 3- to 4-fold increase in mortality risk with these drugs compared to the untreated AD population and a 2- to 3-fold increase compared to the treated population of clinical trials.
Exploring uterine niche: A systemic review on secondary infertility rates, pathophysiological correlations, impact on assisted reproduction technology (ART), and the efficacy of surgical interventions.
Authors: Jayasundara DMCS , Jayawardane IA , Jayasingha TDKM , Weliange SDS
Published: October 2024

Background: The rising trend of cesarean sections worldwide has resulted in an increased incidence of uterine niches, a cavity formed at the cesarean scar site due to impaired tissue healing. Secondary infertility in women with uterine niches is a hot topic in obstetrics and gynecology. Therefore, the current study aims to untwist the link between secondary infertility and uterine niche, exploring the pathophysiological correlations, effects on assisted reproduction technology, and role of surgical interventions in resuming fertility.
Methodology: PubMed, Cochrane Library, Embase, and Science Direct were searched systematically. Rayyan was employed as a semi-automated tool for study selection. Full-text articles in the English language were included. Systematic reviews, meta-analyses, or book chapters were excluded. Newcastle-Ottawa Scale assessed the quality of cohort and case-control studies, while the Cochrane Risk-of-bias tool evaluated randomized controlled trials. Data synthesis followed a thematic analysis.
Results: 35 articles from 3301 studies met the inclusion criteria. Among those, 25 were cohort studies, only one was a randomized controlled trial, and the rest had different study designs. The study quality assessment revealed average to good quality. The incidence of secondary infertility in women with uterine niches ranged from 27.37% (n=95) to 75% (n=16). Decreased residual myometrial thickness, chronic inflammatory changes at the niche site, and fluid accumulation within the niche cavity were identified as leading causes of secondary infertility. The uterine niche adversely affected assisted reproductive outcomes through multiple mechanisms. Various surgical interventions, including hysteroscopy, laparoscopy, or combined surgery, showed differing efficacies in restoring fertility.
Conclusion: The study provides valuable insights regarding the association between secondary infertility and uterine niche. However, smaller sample sizes, retrospective nature of study designs, reliance on observational data, and heterogeneity of study reporting have limited the ability to arrive at solid conclusions. Therefore, we encourage well-designed prospective studies, including randomized controlled trials, to further explore this trending area.
The study protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD4204526319).
Integration of Traditional Medicine Services into Public Health Centers in Indonesia: A Qualitative Study
Authors: Yuniarsih Sri Mumpuni , Padmawati Retna Siwi , Madyaningrum Ema , Widhow Siwi Sri , Mahendradhata Yodi
Published: October 2024

Background: Many people are still using traditional medicine in various countries. This is a challenge for the government because they must effectively manage services, maintain quality, and protect patients. Integrating traditional medicine into public health centers provides safe and quality services. This study aimed to explore the perceptions and experiences of traditional medicine users and program implementers in Indonesian public health centers.
Methods: This study used an exploratory qualitative research design. Data were collected from program implementers and traditional medicine users. Data were collected through focus group discussions and in-depth interviews from March to June 2023. The study had 16 participants included 10 implementers in focus group discussions and six users in in-depth interviews. analysis with an inductive approach was employed.
Results: Three themes were identified, namely, user preferences for using traditional medicine, success factors of integration, and challenges for improvement of existing integration. Despite obstacles, many participants expressed their support for integration, particularly in terms of human resource readiness. Moreover, people tended to prefer traditional medicine services provided in public health centers over traditional healers because of individual belief, trust in the delivery services, and therapeutic effects.
Conclusion: The integration of traditional medicine services into public health centers is essential to provide easy access and preserve traditional health services that are in line with local wisdom, effective, and safe.
Magnitude and Determinants of knowledge of ovulatory period among young women in Somalia: multilevel analysis using 2020 SHDS
Authors: Ali abdirahman Omer
Published: October 2024

Introduction Ovulation is a key indicator of fertility and understanding its cycle is crucial for natural family planning. Despite its importance, knowledge of the ovulatory cycle (KOC) remains low among women, leading to unintended pregnancies.Methodology This study uses data from the 2020 Somalia Health and Demographic Survey (SHDS) to assess KOC among young Somali women. A multilevel binary logistic regression analysis was conducted to identify determinants of KOC.Results The prevalence of correct KOC was 21.83%. Factors positively associated with correct KOC included older age, higher education, and rural residency. Media exposure showed mixed effects on KOC.Discussion The study highlights a significant knowledge gap in Somalia, consistent with global trends. Regional factors and media content influence KOC. Interventions should target both individual and community levels, focusing on education and tailored media messages.Conclusion Enhancing KOC among young women in Somalia is vital for reducing unintended pregnancies and improving reproductive health. Addressing educational and regional disparities is essential for effective intervention strategies.