bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender-based variations in surgical management of colorectal liver metastases: comprehensive analysis
Authors: Koch Pia F. , Ludwig Kristina , Hillebrandt Karl H. , Freitag Hannes , Blank Moritz , Knitter Sebastian , Modest Dominik Paul , Krenzien Felix , Lurje Georg , Schöning Wenzel , Pratschke Johann , Sauer Igor M. , Moosburner Simon , Raschzok Nathanael
Published: February 2025

Background

Colorectal cancer with liver metastasis affects both men and women. However, therapeutic strategies and long-term outcomes could be influenced by patients’ sex, due to variations in tumour biology, lifestyle, and dietary habits. By conducting a comprehensive comparative analysis, this study aims to detail differences in tumour characteristics, postoperative complications, recurrence rates, and survival outcomes between sexes.

Methods

Single-centre retrospective analysis between 2010 and 2022 of all patients undergoing liver surgery for colorectal liver metastases (CRLM) at the Department of Surgery, Charité– Universitätsmedizin Berlin. Patients were stratified by sex. Statistical analysis was performed using RV4.2.

Results

We analysed 642 patients who underwent hepatic resections for CRLM. Baseline patient characteristics were comparable between sexes: However, significant differences (p < 0.001) were noted in body mass index (BMI), with females exhibiting lower BMIs (median BMI in females: 23.7 kg/m² vs. males: 26.5 kg/m²). Primary tumour locations varied significantly (p = 0.008), with females presenting more sigmoid colon tumours (37%), while males predominantly had rectal tumours (35%). RAS mutation rates were higher in females (54%) than males (34%, p = 0.005). A higher prevalence of bilobar metastases were evident in men (62%, p = 0.011), yet surgical techniques and complications showed comparable distributions. The time for resection was longer in males (median 304 min vs. 290 min in females); however, conversion to open surgery took place more often in females (5.2% vs. 2.3% in males). Postoperative complications and survival rates showed no significant differences by patients’ sex.

Conclusion

Distinct sex-related patterns in tumour characteristics and postoperative outcomes in patients with CRLM were observed, emphasizing the need for further investigations to understand and address gender-based disparities for more personalized clinical management in the future.

Trial registration

This research was conducted with ethical approval from the relevant institutional review board Ethikkommission der Charité– Universitätsmedizin Berlin’ (reference numbers EA2/006/16 and EA4/084/17). No other registration applied.
Presence of TMD-related pain and symptoms associated with anxiety in Peruvian students in their final years of dental education: an analytical cross-sectional study under a multivariable regression model
Authors: Angeles-García Karen , Ladera-Castañeda Marysela , Castro-Ramirez Leonor , Paucar-Rodríguez Elizabeth , Castro-Rojas Miriam , Cervantes-Ganoza Luis , Cayo-Rojas César
Published: February 2025

Background

Temporomandibular disorders (TMD) are frequently associated with anxiety, as this can increase the hyperactivity of the masticatory muscles, resulting in TMD-related pain and symptoms. The aim of this study was to assess the presence of TMD-related pain and symptoms associated with anxiety levels in Peruvian students in their final years of dental education.

Methods

This analytical cross-sectional study of 273 Peruvian students in the final two years of dental education was conducted from October to December 2023. The Zung test was employed to diagnose anxiety, while the TMD-Pain Screener questionnaire was utilized to diagnose painful temporomandibular disorders (TMD). A Poisson regression model with robust variance using Adjusted Prevalence Ratio (APR) was employed to assess the prevalence of TMD-related pain and symptoms. The following variables were considered in the analysis: anxiety, sex, age, academic year, marital status, area of residence, type of housing, living with parents, and occupation. All statistical tests were conducted with a significance level of p < 0.05.

Results

The prevalence of TMD-related pain and symptoms was 24.5%. The 0.7% of the sample exhibited very extreme levels of anxiety; 8.1% demonstrated severe anxiety; and 39.9% exhibited mild to moderate anxiety. Furthermore, dental students with severe to very extreme anxiety and with mild to moderate anxiety were 8.2 times and 3.8 times, respectively, more likely to present TMD-related pain and symptoms (APR = 8.18, 95% CI: 4.62–14.47 and APR = 3.84, 95% CI: 2.18–6.75, respectively), compared to those who did not have anxiety. Conversely, no significant association was observed between the presence of TMD-related pain and symptoms and sex, age, academic year, marital status, area of residence, type of housing, living with parents, or occupation (p > 0.05).

Conclusion

Almost a quarter of the students in their final years of dental education had TMD-related pain and symptoms. It was found that as the level of anxiety increased, from mild to moderate and from severe to very extreme, the likelihood of experiencing TMD-related pain and symptoms also increased significantly. On the other hand, gender, age, academic year, marital status, area of residence, type of housing, living with parents or occupation were not found to be influential factors in the presence of TMD-related pain and symptoms.
A whole-body atlas of BMP signaling activity in an adult sea anemone
Authors: Knabl Paul , Mörsdorf David , Genikhovich Grigory
Published: February 2025

Background

BMP signaling is responsible for the second body axis patterning in Bilateria and in the bilaterally symmetric members of the bilaterian sister clade Cnidaria—corals and sea anemones. However, medusozoan cnidarians (jellyfish, hydroids) are radially symmetric, and yet their genomes contain BMP signaling components. This evolutionary conservation suggests that BMP signaling must have other functions not related to axial patterning, which keeps BMP signaling components under selective pressure.

Results

To find out what these functions might be, we generated a detailed whole-body atlas of BMP activity in the sea anemone Nematostella. In the adult polyp, we discover an unexpected diversity of domains with BMP signaling activity, which is especially prominent in the head, as well as across the neuro-muscular and reproductive parts of the gastrodermis. In accordance, analysis of two medusozoan species, the true jellyfish Aurelia and the box jellyfish Tripedalia, revealed similarly broad and diverse BMP activity.

Conclusions

Our study reveals multiple, distinct domains of BMP signaling in Anthozoa and Medusozoa, supporting the versatile nature of the BMP pathway across Cnidaria. Most prominently, BMP signaling appears to be involved in tentacle formation, neuronal development, and gameto- or gonadogenesis.
The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts
Authors: Masi Ilenia , Ottavi Flavia , Caprara Valentina , Rio Danila Del , Kunkl Martina , Spadaro Francesca , Licursi Valerio , Tuosto Loretta , Bagnato Anna , Rosano’ Laura
Published: February 2025

Background

The invasive and metastatic spread of serous ovarian cancer (SOC) results from the cooperative interactions between cancer and stroma, which include extracellular matrix (ECM) and cellular components, including cancer-associated fibroblasts (CAFs). Soluble factors secreted by cancer and stromal cells contribute to stroma remodeling through the secretion of ECM proteins, providing a favorable environment for cancer cell dissemination. The peptide endothelin-1 (ET-1), through two G protein-coupled receptors (GPCR), endothelin receptor type A (ETAR) and B (ETBR), acts on both cancer and stromal cells, engaging the protein β-arrestin1 (β-arr1), to bolster SOC progression. However, its role in the regulation of the ECM proteins by ovarian fibroblasts is not understood. This study delves into the role of ET-1 as a regulator of type I collagen (Col1) and fibronectin (FN).

Methods

We used human primary ovarian fibroblasts (HOFs) and CAFs. The expression of Col1 (COL1A1) and FN (FN1) were detected by western blotting (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and confocal laser scanning microscopy (CLSM) in cells and tumor tissue sections from mice xenografts, while the transcription of COL1A1 was detected by luciferase reporter gene assay. The nuclear function of β-arr1 was evaluated by silencing and rescue expression with wild-type (WT) and nuclear mutant plasmid constructs, RNA seq and differential gene expression and gene sets enrichment analyses. The prognostic role of COL1A1, FN1, EDN1 (ET-1) and ARRB1 (β-arr1) gene expression was evaluated using the Kaplan–Meier plotter database and clinical ovarian cancer tissue samples.

Results

We demonstrated that ET-1 boosts Col1 and FN expression in HOFs, akin to ovarian CAF levels. Both receptors are implicated, evident from inhibitory effects after ETAR or ETBR antagonist treatments and notably with bosentan, a dual antagonist, in vitro and in vivo. At the molecular level, ET-1 triggers the activation of COL1A1 promoter activity and its enhanced expression via β-arr1 nuclear function. Transcriptome analysis of β-arr1-silenced HOFs confirms the nuclear role of β-arr1 in collagen and ECM remodeling-related protein transcriptional regulation. Accordingly, a high level of EDN1/ARRB1 expression in combination with either COL1A1 or FN1 is associated with the poor prognosis of SOC patients.

Conclusions

These findings hint at ET-1 involvement in ECM remodeling and early SOC stages by modulating the expression of Col1 and FN. Targeting ET-1 signaling with ETAR/ETBR antagonists might interfere with the ability of CAFs to produce key ECM proteins in this tumor.
A blue blood toddler– a case report of methemoglobinemia and literature review
Authors: Pjetraj Dorina , Mechri Madiha El , Bacelli Silvia , Fabiani Elisabetta , Caponi Laura , Gatti Simona , Lionetti Elena
Published: February 2025

Background

Methemoglobinemia (MetHb) is a rare and potentially life-threatening condition caused by oxidation of ferrous hemoglobin (Fe2+) to the ferric (Fe3+) state, making it incapable of binding oxygen and resulting in cyanosis and tissue ischemia.

Case presentation

This case presentation describes a 1-year-old boy who developed sudden cyanosis and reduced consciousness disorder. An initial assessment showed decreased oxygen saturation (SpO2 85%) despite oxygen therapy, while point-of-care venous blood gas (VBG) analysis assessed high rates of MetHb (72.7%). Methylene blue and ascorbic acid were administered, resulting in in rapid clinical recovery and normalized VBG test results. The trigger for this condition was not identified, however the most likely cause of poisoning was attributed to food oxidants.

Conclusion

Starting from the description of a clinical case, this paper discusses the causes and mechanisms of possible poisoning and reviews recent guidelines for methemoglobinemia management.
Establishment and validation of risk prediction model to predict intravenous immunoglobulin-resistance in Kawasaki disease based on meta-analysis of 15 cohorts
Authors: Wang Shuhui , Sun Na , Liu PanPan , Qian Weiguo , Xu Qiuqin , Yang DaoPing , Zhang Mingyang , Hou Miao , Chen Ye , Qian Guanghui , Gao Chunmei , Sun Ling , Lv Haitao
Published: February 2025

Background

Pediatric Kawasaki disease (KD) patients showing resistance to intravenous immunoglobulin (IVIG) are at risk of coronary artery lesions; thus, early prediction of IVIG resistance is particularly important. Herein, we aimed to develop and verify a novel predictive risk model for IVIG resistance in KD based on meta-analyses.

Methods

PubMed, Embase, and Web of Science databases were searched for cohort studies on the risk factors for IVIG resistance from January 2006 to December 2022. Data were extracted from the screened literature, followed by quality assessment using the Newcastle-Ottawa scale. meta-analyses used Stata 17.0 software to extract the risk factors with significant combined effect sizes and combined risk values, followed by logistic regression prediction model construction. The model was prospective validated using data from 1007 pediatric KD cases attending the Children’s Hospital of Soochow University. The model’s predictive ability was assessed using the Hosmer–Lemeshow test and area under the receiver operating characteristic curve (AUC) and the clinical utility was assessed using decision curve analysis(DCA).

Results

Fifteen cohort studies reporting 4273 patients with IVIG resistance were included. The incidence of IVIG resistance was 16.2%. Six risk factors were reported ≥ 3 times with significant results for the combined effect size: male sex, rash, cervical lymphadenopathy, % neutrophils ≥ 80%, Age ≤ 12 months and platelet count ≤ 300 × 109/L. The logistic scoring model had 83.8% specificity, 70.4% sensitivity, and an optimal cut-off value of 23.500.

Conclusion

The risk prediction model for IVIG resistance in KD showed a good predictive performance, and pediatricians should pay high attention to these high-risk patients and develop an appropriate individual regimens to prevent coronary complications.
Analysis of informed consent forms of patients undergoing cancer genetic testing in the era of next-generation sequencing
Authors: Kerševan Tina , Kogovšek Tina , Blatnik Ana , Krajc Mateja
Published: February 2025

Background

The Department of Clinical Cancer Genetics at the Institute of Oncology Ljubljana offers genetic counselling and testing to cancer patients and their relatives. Before undergoing genetic testing, patients sign the informed consent form. In addition to giving consent for collection of biological material and genetic testing, patients decide about storage of biological material and participation in international databases. Furthermore, patients decide whether the information regarding their test results may be revealed to their blood relatives and whether they want to be informed about secondary findings.

Methods

Using the signed consent forms, we investigated the effect of selected factors on patients’ decisions. Using different statistical methods, we tried to determine the proportion of patients who opted for different items and the effect of gender, age and cancer diagnoses on their decisions.

Results

Nearly all (99.6%) patients, regardless of gender, age, and presence of oncological diagnosis, consented to the storage of their biological material, 98.4% of patients, regardless of gender, age, and presence of oncological diagnosis, wanted to be included in international databases in a pseudo-anonymised form, 98.8% of patients, irrespective of gender, age, and presence of oncological diagnosis, allowed blood relatives to see their results, and 98.4% of patients, irrespective of gender, age and presence of oncological diagnosis, wanted to know whether secondary findings were detected when genetic analysis of their biological material was performed. Men are, on average, more likely to consent but the difference between genders is not statistically significant. Patients without oncological disease were more likely to agree to be included in international databases than patients with a confirmed oncological diagnosis.

Conclusions

Our results show that the vast majority of patients were in favour of the options they were offered. Most importantly, the majority of them allow their genetic test results be revealed to their blood relatives when needed and would participate in international databases. Research in rare diseases, including rare cancer genetic predisposition syndromes, is crucial for optimal diagnostic, prevention and treatment options for patients with rare genetic disorders. The results are also important for refining the approach to pre-and post-test cancer genetic counselling.
Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999–2002
Authors: Daredia Saher , Khodasevich Dennis , Gladish Nicole , Shen Hanyang , Nwanaji-Enwerem Jamaji C. , Bozack Anne K. , Needham Belinda L. , Rehkopf David H. , Deardorff Julianna , Cardenas Andres
Published: February 2025

Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation (

$$B$$

B

= − 0.10 years, 95% CI: − 0.19, − 0.02). No associations were observed for menarche timing. This suggests a connection between earlier menopause and biological aging, with potential clinical implications for identifying those at high risk for age-related disease.
Hereditary multiple exostoses: an educational review
Authors: Rueda-de-Eusebio Alvaro , Gomez-Pena Sara , Moreno-Casado María José , Marquina Gloria , Arrazola Juan , Crespo-Rodríguez Ana María
Published: February 2025

Hereditary multiple exostoses (HME), an autosomal dominant disorder with an incidence of 1:50,000 to 1:100,000, is characterised by the formation of multiple osteochondromas arising from the metaphyses of long and flat bones. These osteochondromas often present as painless palpable lumps, though some cases are symptomatic due to mechanical compression or bursitis. Diagnosis of HME is typically clinical and radiological. WHO diagnostic criteria include ≥ 2 radiological osteochondromas in the juxta-epiphyseal region of the long bones. Genetic testing is reserved for ambiguous cases. HME is associated with mutations in the EXT-1 (exostosin-1) and EXT-2 (exostosin-2) genes. Imaging techniques, including conventional radiography, CT, MRI, ultrasound, and nuclear medicine, play a crucial role in diagnosing and assessing HME, with each modality offering distinct advantages in visualising the lesions and associated complications. Common complications include skeletal deformities, fractures, bursitis, as well as neural and vascular abnormalities. Notably, there is a 10% risk of malignant transformation into secondary chondrosarcoma in HME patients, compared to only a 1% risk in those with solitary osteochondromas. Malignant transformation should be suspected in patients with new-onset pain or specific imaging features in an osteochondroma, such as growth of de cartilaginous cap. In these cases, an MRI should be performed to assess the cartilage cap thickness. Advances in imaging techniques and genetic understanding have improved the management and prognosis of HME. Follow-up is essential to rule out malignant transformation. This review summarises current knowledge on the clinical presentation, pathogenesis, imaging characteristics, complications, and treatment of HME.

Critical relevance statement

HME is a disorder characterised by the formation of osteochondromas arising from long and flat bones. Multi-modality imaging characteristics, clinical presentation, complications, and treatment are highlighted to familiarise the readers with this entity and offer optimal patient care.

Key Points

HME is characterised by multiple osteochondromas on long and flat bones.

Imaging for HME includes radiography, CT, MRI, ultrasound, and nuclear medicine studies.

Complications include non-malignant complications, such as bone deformities and malignant transformation.

Cartilage-cap measurement with MRI or US is key to exclude malignancy.

Follow-up is essential to rule out malignant transformation of the osteochondromas.

Graphical Abstract
Gain of 20q11.21 in human pluripotent stem cells enhances differentiation to retinal pigment epithelium
Authors: Vitillo Loriana , Anjum Fabiha , Hewitt Zoe , Laing Owen , Ababneh Nidaa A. , Baker Duncan , Barbaric Ivana , Coffey Peter J.
Published: February 2025

Background

Cell therapies based on human pluripotent stem cells (hPSCs) are in clinical trials with the aim of restoring vision in people with age-related macular degeneration. The final cell therapy product consists of retinal pigment epithelium (RPE) cells differentiated from hPSCs. However, hPSCs recurrently acquire genetic abnormalities that give them an advantage in culture with unknown effects to the clinically-relevant cell progeny. One of the most common genetic abnormalities in hPSCs is the sub-karyotype 20q11.21 copy number variant, known to carry oncogenes. Understanding the impact of this variant on RPE differentiation and its potential for malignant transformation is crucial for the development of safe and effective cell therapies.

Methods

We monitored the RPE differentiation efficiency of hPSCs with or without the 20q11.21 variant. We then phenotyped the purified RPE cells for functionality, purity and tumorigenicity potential.

Results

We observed that 20q11.21 clones exhibited an enhanced differentiation capacity, developing pigmented foci at a higher rate and yield compared to normal clones. Gene expression analysis confirmed the upregulation of key RPE markers in 20q11.21 clones. The enhanced differentiation capacity of 20q11.21 clones was found to be dependent on the activity of BCL-XL, located within the amplicon. Furthermore, we demonstrated that 20q11.21-containing RPE cells displayed a mature phenotype, maintained long-term stability, and exhibited no malignant transformation capacity in vitro.

Conclusion

We demonstrated that gain of 20q11.21 enhances the speed and yield of RPE differentiation without compromising the phenotype of the derivatives. Finally, we discovered that 20q11.21-localised BCL-XL is important for RPE differentiation with potential non-canonical roles in retinal biology.
Implementing intranasal povidone-iodine in the orthopedic trauma surgery setting to prevent surgical site infections: a qualitative study of healthcare provider perspectives
Authors: Racila AM , Balkenende Erin C. , Herwaldt Loreen A. , Willey Michael C. , Boyken Linda D. , Pottinger Jean G. , Ayers Brennan S. , Dukes Kimberly C. , Ward Melissa A. , Schweizer Marin L.
Published: February 2025

Background

Surgical site infections (SSIs) are associated with morbidity, mortality, and increased costs. Staphylococcus aureus is the most common cause of SSIs and approximately 30% of hemodialysis patients carry this organism in their nares. Unlike mupirocin, intranasal povidone-iodine (PVI) is applied only the day of surgery to prevent surgical site infections. Thus, intranasal PVI could be valuable in orthopedic trauma surgery settings where time to prepare a patient for surgery is limited.

Methods

We conducted a small phase IV post-marketing study from 2020 to 2021 in an academically affiliated hospital wherein staff administered intranasal PVI pre- and post-operatively to consenting patients undergoing orthopedic fixation procedures for traumatic fractures. Before implementing the PVI intervention, we conducted a human factors task analysis to determine the optimal time and hospital location to perform PVI decolonization for patients receiving these orthopedic fixation procedures. After the post-marketing study was completed, we conducted qualitative interviews with healthcare staff to determine barriers and facilitators that could affect staff members’ likelihood of administering PVI to patients. We aligned our inductive interview findings with strategies defined in Powell and colleagues’ Expert Recommendations for Implementing Change (ERIC) framework to facilitate generalizability and standardized reporting of implementation strategies.

Results

Our human factors task analysis identified the Day of Surgery Admissions (DOSA) as the appropriate context for PVI administration within surgical workflow, as there was downtime during this period and direct patient-provider communication could occur. Two DOSA nurses, one postoperative nurse, and one orthopedic trauma surgeon agreed to be interviewed. Facilitators of intranasal PVI administration included emphasizing the non-invasiveness of PVI nasal swabs to patients and emphasizing intranasal PVI efficacy to staff and patients. While the nurse participants felt that having PVI orders with other medication orders in the EMR helped them identify patients enrolled in the study and who required PVI, entering these orders increased the surgeon’s workflow and presented a time barrier.

Conclusions

Macro- and micro-level contextual factors should be considered when tailoring implementation to healthcare settings. Our findings reinforce prior work demonstrating the value of incorporating human factors engineering methodologies into infection control and prevention implementation approaches.
Effectiveness of perioperative remimazolam in preventing postoperative delirium: a systematic review and meta-analysis
Authors: Wang Mingzhen , Liu Jinhui , Liu Wenjie , Zhang Xin , Zhang Gaofeng , Sun Lixin , Bi Yanlin , Wang Hong , Dong Rui
Published: February 2025

Background

To compare the POD rates in patients undergoing non-cardiac surgery who received remimazolam perioperatively versus placebo or other sedatives.

Methods

We systematically searched four major databases (Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed) for relevant randomized controlled trials (RCTs) up to July 11, 2024. Literature quality evaluation was used the bias risk table in Review Manager 5.4. The primary outcome of interest was POD, and secondary outcomes were the hypotension risk, bradycardia and, nausea and vomiting.

Results

Across 11 trials involving 1985 participants, we recorded 309 cases of POD during follow-up. In trials where the control group received saline, remimazolam decrease the risk of POD significantly by 70% (RR 0.30, 95% CI [0.19, 0.46]; p < 0.00001). Statistical analysis did not show significant difference in the risk of POD between the remimazolam group and the groups receiving either dexmedetomidine (RR 1.23 [0.64, 2.37]; p = 0.53) or propofol (RR 0.83 [0.60, 1.16]; p = 0.28). Regarding adverse events, remimazolam significantly reduces the morbidity of hypotension compared to dexmedetomidine (RR 0.25 [0.10, 0.65]; p = 0.004) and propofol (RR 0.45 [0.33, 0.60]; p < 0.00001). In addition, there were no significant differences in the incidence of bradycardia (RR 0.85; 95% CI [0.34–2.12], p = 0.72) and nausea and vomiting (RR 1.06; 95% CI [0.74–1.51], p = 0.77) between remimazolam and the control group.

Conclusions

During the perioperative period, using remimazolam can lower POD risk after surgery for patients who had non-cardiac surgery, but remimazolam does not work better than dexmedetomidine or propofol. Compared with the dexmedetomidine and propofol, remimazolam also has apparent advantages in preventing intraoperative hypotension.
Secular Trends in Hip Fracture Mortality and Predictors of Mortality from the NSQIP Database
Authors: Rhayem Caline , Ghosn Aya , Issa Zeinab Ali , Alwan Joudie Sahar , Dimassi Hani , Haidar Rachid , Fuleihan Ghada El-Hajj
Published: February 2025

Context

Hip fractures incur high morbidity and mortality. Data on secular trends in mortality from hip fractures and risk predictive models are scarce.

Objective

We aim to describe secular trends in 30-day mortality post-hip fracture surgery from the 2011-2017 National Surgical Quality Improvement Program (NSQIP) database, identify preoperative and on-discharge predictors of 30-day mortality and develop risk calculators.

Methods

We calculated yearly proportions of deaths and examined survival using Kaplan Meier curves. We implemented logistic regressions models, using SPSS and created calculators using Excel.

Results

In 84,824 cases of hip fracture surgery, the overall 30-day mortality was 6.8%. It decreased from 8.1% to 6.5% between 2011 and 2017 (p<0.001). Significant preoperative predictors of 30-day mortality on admission were male gender, age, lower BMI, white race, poorer functional health status, higher creatinine, lower hematocrit, >10% weight loss in the past 6 months, congestive heart failure within 30 days before surgery, and chronic obstructive pulmonary disease. Predictors on discharge included preoperative predictors with the exception of white race, hematocrit and > 10% weight loss in the past 6 months, and the addition of unplanned intubation, cerebrovascular accident, myocardial infarction, and pneumonia. The parsimonious preoperative risk calculator for mortality had 10 variables, an area under the curve (AUC) of 0.739, and a model fit R2 of 0.9716. The on-discharge calculator had 11 variables, an AUC of 0.800, and an R2 of 0.9924.

Conclusion

30-day mortality post-hip fracture surgery decreased significantly from 2011 to 2017. Readily available clinical risk factors predict mortality, preoperatively and on discharge. While most predictors are non-modifiable, the calculators may better inform clinical decision-making.
Spatio-temporal reconstruction of gene expression patterns in developing mice
Authors: Aviñó-Esteban Laura , Cardona-Blaya Heura , Sharpe James
Published: February 2025

Understanding gene regulation in organism development is crucial in biology. Techniques like whole-mount in situ hybridization can reveal spatial gene expression in organs and tissues. However, capturing time-lapse movies of gene expression dynamics in embryos developing in utero, such as mice, remains technically challenging beyond the early stages. To address this, we present a method to integrate static snapshots of gene expression patterns across limb developmental stages, creating a continuous 2D reconstruction of gene expression patterns over time. This method interpolates small tissue regions over time to create smooth temporal trajectories of gene expression. We successfully applied it to a number of key genes in limb development, including Sox9, Hand2, and Bmp2. This approach enables a detailed spatio-temporal mapping of gene expression, providing insights into developmental mechanisms. By estimating gene expression patterns at previously unobserved time points, it facilitates the comparison of these patterns across samples. The reconstructed trajectories offer high-quality data that will be useful to guide computational modeling and machine learning, advancing the study of developmental biology in systems where real-time imaging is technically difficult or impossible.
Unraveling the etiology of primary amenorrhea: Insights from a tertiary care center in Peshawar, Pakistan
Authors: Ambareen Samad  , Bangash Arzoo Gul , Talat Naz
Published: February 2025

Background & Objectives: The onset of menstruation heralds the beginning of feminism and fecundity. Primary amenorrhea is a distressing symptom and is often associated with late diagnosis and appropriate management. Our study aimed to find the frequency of primary amenorrhea along with its causes and subsequent management by a multidisciplinary team.
Methods: In our descriptive case series patients presenting with primary amenorrhea to the Department of Gynaecology, Khyber Teaching Hospital Peshawar from January 2018 to December 2022, were included. Gynecologist initially analyzed the cases based on history, clinical examination (secondary sexual characteristics, Body mass index) and relevant investigations including hormonal profile, pelvic ultrasound, MRI and karyotype. After final diagnosis, a multidisciplinary team comprising of plastic surgeon, endocrinologist and psychiatrist advised treatment based on cause. Relevant information was recorded on predesigned proforma. Data was analyzed using SPSS 23.
Results: The frequency of primary amenorrhea was 0.3% out of 18,504 patients seen in Gynaecology clinic. Forty-six (82%) patients were in the age group of 14-20 years. The mean body mass index was 22.8±2.4. Mullerian agenesis was seen in 22(39%) of patients, 20(35.7%) had outflow tract abnormality which were treated by vaginoplasty or hymenectomy/ resection of vaginal septum depending on cause. Ten (17.8%) patients diagnosed with gonadal dysgenesis. Four (7.1%) patients with constitutionally delayed menarche had spontaneous onset of menstruation.
Conclusions: Disorders related to Mullerian agenesis are the most common cause of primary amenorrhea. Timely diagnosis by attending gynecologist and subsequent multi-modal approach, including psychological counseling, hormonal therapy, and tailored surgical interventions like neovagina creation by vaginoplasty, hymenectomy and laparoscopic gonadectomy can ensure appropriate management of this distressing condition in young girls.
doi: https://doi.org/10.12669/pjms.41.3.11199
How to cite this: Samad A, Bangash AG, Naz T. Unraveling the etiology of primary amenorrhea: Insights from a tertiary care center in Peshawar, Pakistan. Pak J Med Sci. 2025;41(3):872-875. doi: https://doi.org/10.12669/pjms.41.3.11199
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correlation between social media addiction and academic procrastination in medical students at public and private medical colleges at Peshawar
Authors: Naushad Khurram , Jamil Brekhna , Naveed Afzal Khan  , Maidha Jadoon
Published: February 2025

Objective: The study aim was to assess correlation between social media addiction and academic procrastination among medical students at public and private medical colleges in Peshawar.
Methods: A correlational research design was employed with research protocols approved by the Advance Studies and Research Board of Khyber Medical University. Data were collected from two public and five private medical colleges. Universal sampling was then performed. Of 4716 medical students, 3366 participated in the study, with a response rate of 71.4%. This study was conducted between June and December 2023. Data were collected using the structured social media addiction scale (SMAS) and academic procrastination scale (APS).
Results: Male participants were (1775) 52.7%, and the rest (1591) 47.3% were female. Among the responders (1591) 61% resided in hostels. The mean academic achievement was 74.14%, ranging from 30% to 85%. Most medical students (63%) showed moderate and 34% showed high academic procrastination. Majority of the medical students (81%) were social media addicts and male reported higher scores. Social media addiction was highly correlated with academic procrastination (r=0.539), which was regressed and found that 29% (R2=0.289) of social media addiction contributed to academic procrastination. Medical students from the public sector, Android users, third-year students, male students, and hostel residents were more prone to social media addiction and academic procrastination.
Conclusion: Social media addiction prevails among medical students and is highly correlated with academic procrastination. Hostel residents, males, and android users were more addicted to social media than their counterparts.
doi: https://doi.org/10.12669/pjms.41.3.9276
How to cite this: Naushad K, Jamil B, Khan NA, Jadoon M. Correlation between social media addiction and academic procrastination in medical students at public and private medical colleges at Peshawar. Pak J Med Sci. 2025;41(3):837-842.  doi: https://doi.org/10.12669/pjms.41.3.9276
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Whispers of Resilience: A phenomenological exploration of maternal journeys with children affected by Downs Syndrome in Quetta, Baluchistan
Authors: Devi Ambica , Ansari Baig Lubna , Musharraf Mehjabeen , Tariq Hira
Published: February 2025

Background & Objective: Down’s syndrome, a chromosomal disorder, with an incidence of approximately one in 800 live births globally affects physical and intellectual development of a child, having greatest impact on mothers. This study explored the challenges faced by the mothers of children with Down’s Syndrome related to their upbringing at different stages of life.
Methods: Qualitative research was conducted using Phenomenological approach from May 2021- April 2022 in Quetta, Baluchistan. Mothers were selected through purposive sampling from institutional records of Wilderness School, Quetta, the only private school for special children. Five In depth Interviews and two Focus Group Discussions were conducted with 17 mothers using a semi structured interview guide. Data collected in audio files was transcribed verbatim into English language. Analysis was done by two researchers independently.
Results: The themes included, Experience of Giving birth to a child with Down’s Syndrome, Social support system, Personal Challenges, Experiencing Worrisome thoughts about child’s future and Experiencing personality changes. The findings imply that giving birth and bringing up a child with DS is a life-changing process. Social stigmatization, lack of support by family, in-laws, relatives and financial constraints to afford schooling and rehabilitation make it challenging for mothers to provide adequate attention and developmental opportunities to the child. Mothers compromise on their health, career, social life, social status and relationship with other family members.
Conclusion: Raising children with Down syndrome is a life changing process and the absence of prenatal diagnosis in regions like Quetta and limited counseling from concerned doctors leaves mothers unprepared. This results in care givers reliance on internet resources for developing understanding about the syndrome and child care.
doi: https://doi.org/10.12669/pjms.41.3.9710
How to cite this: Devi A, Baig LA, Musharaf M, Tariq H. Whispers of Resilience: A phenomenological exploration of maternal journeys with children affected by Downs Syndrome in Quetta, Baluchistan. Pak J Med Sci. 2025;41(3):856-860. doi: https://doi.org/10.12669/pjms.41.3.9710
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Το συναισθηματικό κλίμα της ελληνικής κοινωνίας και οι στάσεις απέναντι στην ενσωμάτωση των προσφύγων
Authors: Σακελλαρίου Βενετία
Published: February 2025

Σκοπός της διατριβής ήταν η διερεύνηση του συναισθηματικού κλίματος που αναπτύχθηκε στην ελληνική κοινωνία στις κοινωνικοπολιτικές και οικονομικές συνθήκες που έχουν δημιουργηθεί ως συνέπεια της προσφυγικής κρίσης, αλλά και της οικονομικής που προηγήθηκε, των συλλογικών συναισθημάτων που εμπεριέχονται σε αυτό, καθώς και του τρόπου με τον οποίο σχετίζεται με τις στάσεις που υιοθετούν οι πολίτες απέναντι στην ενσωμάτωση των προσφύγων στον αστικό ιστό. Για τη διερεύνηση της σχέσης συναισθηματικού κλίματος και στάσεων και τους παράγοντες που τη διαμεσολαβούν, επιλέχθηκε ένας συνδυασμός ποσοτικής και ποιοτικής έρευνας. Τα αποτελέσματα έδειξαν ότι το συναισθηματικό κλίμα που επικρατεί στην ελληνική κοινωνία είναι αρνητικό, ενώ η συσχέτισή του με τις στάσεις των πολιτών απέναντι στην ενσωμάτωση των προσφύγων είναι θετική. Οι παράγοντες από τους οποίους διέπεται το συναισθηματικό κλίμα είναι η κοινωνική δυσανεξία, που εμπεριέχει την απελπισία και την ανασφάλεια που αισθάνονται οι πολίτες, τα αρνητικά συναισθήματα φόβου και θυμού, η κοινωνική αποξένωση, που σχετίζεται με την απογοήτευση και αρνητικά συναισθήματα για το κοινωνικό σύνολο, καθώς και το συγκρουσιακό δυναμικό. Ένα κύριο χαρακτηριστικό του συναισθηματικού κλίματος που επικρατεί στην ελληνική κοινωνία, όπως προέκυψε από την έρευνα, είναι η ανθεκτικότητά του.
On Greedy-Like Policies in Online Matching with Reusable Network Resources and Decaying Rewards
Authors: Simchi-Levi David , Zheng Zeyu , Zhu Feng
Published: February 2025

We build a unified modeling framework for classical online matching problems and emerging online matching problems with three additional practical features: reusable resources, network resources, and decaying rewards. For online matching problems in the unified framework, we provide a unified performance analysis tool for the greedy policy and its simple variants, which we refer to as greedy-like policies. We prove that greedy-like policies can achieve near-optimal performances for online matching problems in the unified framework, where the policy performance is measured by competitive ratios under adversarial environments. We then analyze several representative special classes of online matching problems, which incorporate additional realistic structural assumptions on top of the unified framework. Specifically, we consider online matching problems with each of the following three additional structures: (i) singleton resources with time-decaying rewards; (ii) network resources with accept/reject decisions; and (iii) network resources with interval-type bundles. We show that for these special classes of online matching problems, slight modifications to greedy-like policies can successfully utilize additional structural information to further enhance policy performances. This work may suggest that the greedy policy and its variants, despite its simplicity, can achieve reliable performances for a number of emerging online matching problems.

This paper was accepted by J. George Shanthikumar, data science.

Funding: The work of D. Simchi-Levi and F. Zhu is partially supported by the Massachusetts Institute of Technology Data Science Laboratory.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2023.02588 .
The Professionalization of Academic Advising in China: From the Perspective of Culture Diversity
Authors: Zhan Yisi , Litip Wuriyeti
Published: February 2025

Despite the emphasis on professionalization of academic advising in global higher education, few scholars have focused on professionalization in a diverse cultural context. This article provides an exploration into the educational history and practices that have led to increasing calls for professionalization of academic advising in Chinese colleges and universities. Specifically, Chinese educational culture differs from Western culture in that it prioritizes social values and government recognition. Scholars can expand their professionalization theory framework through concluding government recognition. Recognizing and appreciating this broad cross-cultural perspective will help practitioners understand Chinese students better and advise them appropriately. It can also help future scholars investigating professionalization on an international or cross-cultural level.
Environmental Harm Resulting from Israeli Bombing of Gaza: Legal Aspects
Authors: Aasi Joni
Published: February 2025

Israel’s unprecedented bombardment of the Gaza Strip has caused more than 100,000 casualties and the forced displacement of most of Gaza’s 2.3 million inhabitants, but there is a “silent victim”: the environment, which includes the natural and built environment. This bombing is part of a strategy adopted by the occupying power toward the Palestinians since 1967, a strategy of conflict management. The high intensity and scale of the bombing is aimed at achieving a period of calm, as was the case after the invasion of the OPT (Operation Defensive Fence, 2002). According to this strategy, the continuation of the occupation of the Gaza Strip requires a radical “mowing” operation, which in legal terms amounts to genocide. This article attempts to present a broad concept of genocide that includes ecocide, and discusses the consideration of “military necessity” in populated areas when we know that the casualty rate in bombing these areas exceeds 90 percent, and that Israel justifies any objective on this principle. It also raises the question of responsibility for ecocide in light of developments in international criminal law and the contradiction between individual and collective responsibility.
Exploring and Comparing Moroccan EFL Writing Instructors’ and University Students’ Perceptions and Reported Practices of Written Feedback
Authors: Mamad Abderrahim
Published: February 2025

A visszajelzésekkel kapcsolatos kutatások az írásbeli visszajelzések hatékonyságát két szempontból vizsgálták az angol mint idegen nyelvi írás kontextusában. A produktumra fókuszáló visszajelzések az elkészült szövegváltozatokra vonatkoznak, míg a folyamatorientált visszajelzések az írási folyamat előtt, közben és után alkalmazhatók. A tanulók és tanárok nézeteit és gyakorlatát főként a produktum-orientált hibajavító visszajelzésekkel kapcsolatban tárták fel, így a két visszajelzési típus összehasonlító elemzése ritkán jelent meg. A disszertáció célja felsőfokú angol nyelvi képzésben résztvevő hallgatók és oktatók produktum- és folyamatalapú visszajelzésekkel kapcsolatos nézeteinek és gyakorlatának feltárása és összehasonlítása az írásbeli szövegalkotás területén. Az értekezés egy szisztematikus áttekintést és három empirikus vizsgálatot tartalmaz. A feltáró kvantitatív vizsgálatokban 468 marokkói egyetemi hallgató és 51 oktató vett részt, az adatfelfelvétel során két saját fejlesztésű kérdőívet alkalmaztunk. Ezek kilenc különböző alskálával fedték le a két visszacsatolási típus jellemzőit, amely több összehasonlítást is lehetővé tett az adatelemzés során. Az első vizsgálat eredményei szerint a hallgatók előnyben részesítették az írásbeli hibajavító visszajelzéseket, valamint olyan konkrét, személyre szabott és részletes tartalomalapú visszajelzéseket, amelyek segítenek azonosítani az írási folyamat következő lépéseit. Ugyanakkor arról is beszámoltak, hogy preferenciáikhoz viszonyítva oktatóik ritkábban alkalmazták ezeket a gyakorlatokat. A második vizsgálatban feltártuk, hogy az oktatók fontosnak tartották az írásbeli hibajavító és tartalomalapú visszajelzések alkalmazását, illetve azt is, hogy lehetővé tegyék a hallgatók számára, hogy hatékony visszajelzési módokon keresztül értékeljék saját és mások munkáját. Bár ezeket a gyakorlatokat az oktatók előnyösnek tartották, mégis a preferenciáikhoz képest ritkábban alkalmazták. A harmadik vizsgálatban arra a következtetésre jutottunk, hogy az oktatók nézetei a folyamat- és produktumalapú visszajelzési technikák használatának fontosságáról összhangban voltak a hallgatók preferenciáival. Az oktatók azonban megítélésük szerint gyakrabban alkalmaztak írásbeli javító visszajelzéseket, valamint a hallgatókat támogató, hatékony visszajelzési módokat az írás folyamatában, mint amennyire a diákjaik érzékelték. A vizsgálatok igazolták a két saját fejlesztésű kérdőív megfelelő pszichometriai tulajdonságait, amelyek alkalmasak a hallgatók és oktatók visszajelzéseivel kapcsolatos nézeteinek és gyakorlatának elemzésére és összehasonlítására. A különböző alskálákból származó eredmények a produktum- és folyamatalapú írásbeli visszajelzések hatékonyságának vizsgálatát is támogathatják.