bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of gastrointestinal bleeding hospitalization risk in hemodialysis using machine learning
Authors: Larkin John W. , Lama Suman , Chaudhuri Sheetal , Willetts Joanna , Winter Anke C. , Jiao Yue , Stauss-Grabo Manuela , Usvyat Len A. , Hymes Jeffrey L. , Maddux Franklin W. , Wheeler David C. , Stenvinkel Peter , Floege Jürgen ,   on behalf of the INSPIRE Core Group, Winter Anke , Zimbelman Justin
Published: October 2024

Background

Gastrointestinal bleeding (GIB) is a clinical challenge in kidney failure. INSPIRE group assessed if machine learning could determine a hemodialysis (HD) patient’s 180-day GIB hospitalization risk.

Methods

An eXtreme Gradient Boosting (XGBoost) and logistic regression model were developed using an HD dataset in United States (2017–2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤ 180 days before GIB hospitalization were classified as positive observations; others were negative. Models considered 1,303 exposures/covariates. Performance was measured using unseen testing data.

Results

Incidence of 180-day GIB hospitalization was 1.18% in HD population (n = 451,579), and 1.12% in testing dataset (n = 38,853). XGBoost showed area under the receiver operating curve (AUROC) = 0.74 (95% confidence interval (CI) 0.72, 0.76) versus logistic regression showed AUROC = 0.68 (95% CI 0.66, 0.71). Sensitivity and specificity were 65.3% (60.9, 69.7) and 68.0% (67.6, 68.5) for XGBoost versus 68.9% (64.7, 73.0) and 57.0% (56.5, 57.5) for logistic regression, respectively. Associations in exposures were consistent for many factors. Both models showed GIB hospitalization risk was associated with older age, disturbances in anemia/iron indices, recent all-cause hospitalizations, and bone mineral metabolism markers. XGBoost showed high importance on outcome prediction for serum 25 hydroxy (25OH) vitamin D levels, while logistic regression showed high importance for parathyroid hormone (PTH) levels.

Conclusions

Machine learning can be considered for early detection of GIB event risk in HD. XGBoost outperforms logistic regression, yet both appear suitable. External and prospective validation of these models is needed. Association between bone mineral metabolism markers and GIB events was unexpected and warrants investigation.

Trial registration

This retrospective analysis of real-world data was not a prospective clinical trial and registration is not applicable.

Graphical Abstract
Antenatal care practices for gestational weight gain: a cross sectional survey of antenatal care providers reported provision and barriers to providing recommended care
Authors: Hollis Jenna L. , Deroover Kristine , Daly Justine , Tully Belinda , Foster Michelle , Lecathelinais Christophe , Pennell Craig E. , Wiggers John , Kingsland Melanie
Published: October 2024

Background

Implementation of recommended gestational weight gain (GWG) care by antenatal care providers is poor. It is unclear whether practice implementation and barriers differ between antenatal care provider profession or experience. This study aimed to assesses the provision of and barriers to guideline care for GWG and examine associations with professional discipline and years of experience.

Methods

A cross sectional survey was conducted with antenatal care providers working in three public maternity services in a regional city in Australia. Data were collected on the provision of and barriers (informed by the Theoretical Domains Framework) to recommended GWG care. Data were summarised using descriptive statistics. Associations between health profession characteristics (professional discipline and years providing antenatal care) and GWG care practices and barrier outcomes were assessed using multivariate logistic regression.

Results

117 antenatal care providers completed the survey (75% participation rate). One quarter (25%) reported that they routinely provided recommended GWG assessment at the first antenatal visit, and 9% at subsequent visits. Only 7% routinely provided recommended advice on GWG, healthy eating and physical activity. Professional discipline or years of experience were not associated with higher odds of GWG practices. Skills, belief about capabilities, belief about consequences and environmental context and resources were barriers to providing care. Medical professionals had higher odds of agreeing that they have been adequately trained to address GWG (OR = 9.14, 95%CI:3.10–26.90) and feel competent in having sensitive conversations with pregnant women about GWG (OR = 8.60, 95%CI:2.29–32.28) than midwives. Midwives had higher odds of agreeing that there are services they can refer pregnant women to for further support (OR = 2.80, 95%CI:1.13–6.91).

Conclusions

The provision of antenatal care for GWG was low, inconsistently provided and did not differ by professional discipline or years of experience. Antenatal care providers report numerous barriers including skills, belief about capabilities, belief about consequences, and environmental context and resources. Barriers to GWG care provision differed by professional discipline, but not years of providing care. The findings demonstrate that the type and prioritisation of practice-change implementation strategies may need to be tailored to address the differential barriers faced by professional groups.
Impact of metadata in multimodal classification of bone tumours
Authors: Hinterwimmer Florian , Guenther Michael , Consalvo Sarah , Neumann Jan , Gersing Alexandra , Woertler Klaus , von Eisenhart-Rothe Rüdiger , Burgkart Rainer , Rueckert Daniel
Published: October 2024

The accurate classification of bone tumours is crucial for guiding clinical decisions regarding treatment and follow-up. However, differentiating between various tumour types is challenging due to the rarity of certain entities, high intra-class variability, and limited training data in clinical practice. This study proposes a multimodal deep learning model that integrates clinical metadata and X-ray imaging to improve the classification of primary bone tumours. The dataset comprises 1,785 radiographs from 804 patients collected between 2000 and 2020, including metadata such as age, affected bone site, tumour position, and gender. Ten tumour types were selected, with histopathology or tumour board decisions serving as the reference standard.

Methods

Our model is based on the NesT image classification model and a multilayer perceptron with a joint fusion architecture. Descriptive statistics included incidence and percentage ratios for discrete parameters, and mean, standard deviation, median, and interquartile range for continuous parameters.

Results

The mean age of the patients was 33.62 ± 18.60 years, with 54.73% being male. Our multimodal deep learning model achieved 69.7% accuracy in classifying primary bone tumours, outperforming the Vision Transformer model by five percentage points. SHAP values indicated that age had the most substantial influence among the considered metadata.

Conclusion

The joint fusion approach developed in this study, integrating clinical metadata and imaging data, outperformed state-of-the-art models in classifying primary bone tumours. The use of SHAP values provided insights into the impact of different metadata on the model’s performance, highlighting the significant role of age. This approach has potential implications for improving diagnostic accuracy and understanding the influence of clinical factors in tumour classification.
Effect of soft tissue volume on midfacial gingival margin alterations following immediate implant placement in the esthetic zone: a 1-year randomized clinical and volumetric trial
Authors: Fettouh Ahmed Ibrahim Aboul , Ghallab Noha Ayman , Ghaffar Khaled Abdel , Elarab Azza Ezz , Abdel-Aziz Nourhan Gamal , Mina Nael Adel , Shemais Nesma Mohamed , Dahab Omnia Aboul
Published: October 2024

Background

The current trial evaluated the midfacial gingival margin changes, volumetric, radiographic and clinical alterations 1-year following immediate implant placement with customized healing abutment (IIP + CHA) either solely, or in combination with xenograft (IIP + Bonegraft) or with connective tissue grafting (IIP + CTG) at sites with thin labial bone in the esthetic zone.

Methods

Thirty-nine non-restorable maxillary teeth indicated for extraction in the esthetic zone were included. Participants were randomly assigned into three equal group; IIP + Bonegraft (Control), IIP + CTG and IIP + CHA. Midfacial gingival margin changes(mm) as primary outcome, labial soft tissue contour change(mm), interdental tissue height changes and total volume(mm3) were assessed. Amount of bone labial to the implant and crestal bone level changes were also recorded. All outcomes were measured 1-year post-operative.

Results

The midfacial gingival margin changes demonstrated a significant difference (P ≤ 0.05) between the groups showing -0.98, -0.74 and -1.54 mm in sites treated with IIP + Bone graft, IIP + CTG and IIP + CHA respectively after1-year. While labial soft tissue contour change (mm), total volume (mm3) and distal interdental tissue height changes (mm) revealed a significant difference after one-year between the studied groups, yet mesial interdental tissue height changes showed no difference (P > 0.05). Both IIP + Bone graft and IIP + CHA groups revealed a significant positive correlation between the total volume loss (mm3) after 1 year and mid-facial gingival margin changes (P ≤ 0.05). However, no significant correlation was observed in the IIP + CTG group (P = 0.63). CBCT measurements showed a significant difference in crestal bone changes between the three groups (P ≤ 0.05), yet, there was no significant difference regarding mean amount of bone labial to the implant(P > 0.05).

Conclusions

This investigation suggests that the mere presence of CTG simultaneous with IIP in the anterior maxilla reduced the midfacial gingival margin alterations (mm), besides, CTG decreased the overall volume loss (mm3) by 5-folds compared to the other studied groups after one year. Meanwhile, using CHA alone with IIP failed to maintain the peri-implant soft tissues contour.

Trial registration

The current trial was retrospectively registered at Clinical trials.gov (ID: NCT05975515, Date: 27-July-2023).
Education about complementary and alternative medicine in cancer self-help groups by trained peers
Authors: Weis Joachim , Jablotschkin Martina , Horneber Markus , Steinmann Diana , Witt Claudia M. , Helmer Stefanie , Bartsch Hans Helge
Published: October 2024

Purpose

On average, about 50% of cancer patients use complementary and alternative medicine (CAM) in addition to conventional cancer treatment. Since there is a high need for information, patients often search for information about CAM and share experiences with peers, especially in self-help groups. In this study, we tested and evaluated an educational concept developed for group leaders of cancer self-help groups on how to approach the topic of CAM in their peer groups.

Methods

The educational concept has been developed and piloted with health care professionals and representatives from different self-help organizations in Germany. It aims to inform and discuss the possibilities and limitations of CAM in terms of scientific evidence, to reflect user behavior, and to provide a guide on how to find and evaluate reliable and evidence-based information sources. First, self-help group leaders took part in an on-site training where they were educated on various CAM topics with the goal of being able to conduct the educational concept in their respective self-help groups. Then, the educated group leaders performed this concept in their groups. The educational concept was evaluated by both the group leaders and participants with respect to acceptance, usefulness, and satisfaction using paper-pencil questionnaires. The study was conducted in Germany based on an observational study design with a six-month follow-up. For the analyses, descriptive and univariate statistics for dependent samples were used.

Results

A total of n = 50 interested group leaders conducted the educational program in their groups. The most common implementation barriers were organizational or structural problems, as well as the feeling of being overwhelmed with managing the program in their groups. A total of n = 423 participants were educated with this program by their respective group leaders. The majority felt satisfied with the educational program and improved their knowledge about CAM. At the six months follow-up (T2), significantly more participants had consulted their physicians to inform themselves about CAM and felt more confident in finding reliable information about CAM.

Conclusions

In this observational study, we have managed to successfully implement an educational concept with respect to the topic of CAM in cancer self-help groups. Based on the results, the concept approach will be modified to include both a CAM- professional and group leader to train the self-help groups. In the future, the effects of the program should be tested by a randomized trial.
Navigating protean career paths in medical education: insights from outstanding medical educators in South Korea
Authors: Lee Bora , Lee Danbi , Shin Hyekyung , Park Sohee , Yang Eunbae B.
Published: October 2024

Background

This study explored the career development experiences of Korean medical educators who have forged their paths amid dynamic medical education landscapes. Additionally, it explored their career development process by introducing a protean career theoretical framework, that is, an individual-led career development theory.

Methods

This study employed Interpretative Phenomenological Analysis (IPA) to gather in-depth insights regarding the experiences of medical educators who have successfully built their careers in Korea. Semi-structured interviews were conducted with nine medical educators to investigate the significance of these experiences. The emerging themes were categorised based on the protean career theory during data analysis.

Results

The findings revealed that medical educators navigated their careers in line with the protean career development model, characterised by protean career orientation, process and outcomes. Their experiences in the medical education domain were aligned with eight factors of the protean career model – self-direction, intrinsic work values, awareness, adaptability, agency, subjective career success, objective career success and organisational commitment.

Conclusion

In the context of less structured career pathways and a rapidly evolving regional environment, medical educators have developed individual-driven careers with self-direction and intrinsic values, formed their identities and demonstrated flexibility and proactive strategies. Hence, the protean career model successfully explains the characteristics of self-directed career development for medical educators, while emphasising the need for organisational support.
CHF6523 data suggest that the phosphoinositide 3-kinase delta isoform is not a suitable target for the management of COPD
Authors: Govoni Mirco , Bassi Michele , Girardello Luca , Lucci Germano , Rony François , Charretier Rémi , Galkin Dmitry , Faietti Maria Laura , Pioselli Barbara , Modafferi Gloria , Benfeitas Rui , Bonatti Martina , Miglietta Daniela , Clark Jonathan , Pedersen Frauke , Kirsten Anne-Marie , Beeh Kai-Michael , Kornmann Oliver , Korn Stephanie , Ludwig-Sengpiel Andrea , Watz Henrik
Published: October 2024

Background

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition. Given patients with COPD continue to experience exacerbations despite the availability of effective therapies, anti-inflammatory treatments targeting novel pathways are needed. Kinases, notably the phosphoinositide 3-kinases (PI3K), are thought to be involved in chronic airway inflammation, with this pathway proposed as a critical regulator of inflammation and oxidative stress response in COPD. CHF6523 is an inhaled PI3Kδ inhibitor that has shown positive preclinical results. This manuscript reports the results of a study of CHF6523 in patients with stable COPD (chronic bronchitis phenotype), and who had evidence of type-2 inflammation.

Methods

This randomised, double-blind, placebo-controlled, two-way crossover study comprised two 28-day treatment periods separated by a 28-day washout. Patients (N = 44) inhaled CHF6523 in one period, and placebo in the other, both twice daily. The primary objective was to assess the safety and tolerability of CHF6523; the secondary objective was to assess CHF6523 pharmacokinetics. Exploratory endpoints included target engagement (the relative reduction in phosphatidylinositol (3,4,5)-trisphosphate [PIP3]), pharmacodynamic evaluations such as airflow obstruction, and hyperinflation, and to identify biomarker(s) of drug response using proteomics and transcriptomics.

Results

CHF6523 plasma pharmacokinetics were characterised by an early maximum concentration (Cmax), reached 15 and 10 min after dosing on Days 1 and 28, respectively, followed by a rapid decline. Systemic exposure on Day 28 showed limited accumulation, with ratios < 1.6 for Cmax and area under the curve from 0 to 12 h post-dose, and with steady state achieved on Day 20. Target engagement was confirmed by a significant 29.7% reduction from baseline in induced sputum PIP3 (29.5% reduction vs. placebo; adjusted ratio 0.705 [0.580, 0.856]; p = 0.001), but this did not translate into an anti-inflammatory pharmacodynamic effect, as assessed through measures including biomarkers and multi-omics. Additionally, although CHF6523 was generally well-tolerated, 95.2% of patients reported cough as an adverse event, most mild to moderate and resolving within one-hour post-dose.

Conclusions

These data, together with those from other PI3K inhibitors, suggest that PI3Kδ is not a suitable pathway for the management of COPD, as the achieved target engagement did not translate into any pharmacodynamic anti-inflammatory effect.

Trial registration

ClinicalTrials.gov (NCT04032535); posted 23rd July 2019.
Weight loss, changes in body composition and inflammatory status after a very low-energy ketogenic therapy (VLEKT): does gender matter?
Authors: Muscogiuri Giovanna , Verde Ludovica , Frias-Toral Evelyn , Reytor-González Claudia , Annunziata Giuseppe , Proganò Mattia , Savastano Silvia , Simancas-Racines Daniel , Colao Annamaria , Barrea Luigi
Published: October 2024

Background

Considering differences in body composition and inflammatory status between sexes, as well as recent recommendations advocating for personalized dietary approaches, this study aimed to explore how sex influences weight loss, changes in body composition, and inflammatory status in subjects with grade I and II obesity undergoing a 45-day of the Very Low-Energy Ketogenic Therapy (VLEKT).

Methods

Participants (21 premenopausal females and 21 males), included in the study adhered to the 45-day of the VLEKT and underwent assessments of anthropometric parameters (weight, height, body mass index—BMI –, and waist circumference), body composition via bioelectrical impedance analysis, and inflammatory status measured by high sensitivity C-reactive protein (hs-CRP) levels at baseline and post-intervention.

Results

At baseline, premenopausal females and males did not differ in BMI (p = 0.100) and hs-CRP levels (p = 0.948). Males demonstrated overall larger benefits than premenopausal females from the VLEKT in terms of weight loss (Δ% = − 11.63 ± 1.76 vs − 8.95 ± 1.65 kg, p < 0.001), fat mass (Δ% = − 30.84 ± 12.00 vs -21.36 ± 4.65 kg, p = 0.002), and hs-CRP levels (Δ% = − 41.42 ± 21.35 vs − 22.38 ± 17.30 mg/L, p = 0.003). Of interest, in males phase angle values are statistically improved compared to female (Δ% = 17.11 ± 9.00 vs 7.05 ± 3.30°, p < 0.001).

Conclusion

These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs.

Graphical Abstract
Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort
Authors: Dahlberg Alma , Tydén Helena , Jöud Anna Saxne , Kahn Fredrik , Berthold Elisabet
Published: October 2024

Background

There is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.

Methods

Autoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.

Results

During the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.

Conclusions

Individuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.
Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury
Authors: Chen Zhangying , Ford Kacie P. , Islam Mecca B. A. R. , Wan Hanxiao , Han Hyebin , Ramakrishnan Abhirami , Brown Ryan J. , Villanueva Veronica , Wang Yidan , Davis Booker T. , Weiss Craig , Cui Weiguo , Gate David , Schwulst Steven J.
Published: October 2024

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people.
Treatment of mild to moderate community-acquired pneumonia in previously healthy children: an Italian intersociety consensus (SIPPS-SIP-SITIP-FIMP-SIAIP-SIMRI-FIMMG-SIMG)
Authors: Donà Daniele , Brigadoi Giulia , Grandinetti Roberto , Pedretti Laura , Boscarino Giovanni , Barbieri Elisa , Matera Luigi , Mancino Enrica , Bergamini Marcello , Castelli Gattinara Guido , Chiappini Elena , Doria Mattia , Galli Luisa , Guarino Alfredo , Lo Vecchio Andrea , Venturini Elisabetta , Marseglia Gianluigi , Verga Maria Carmen , Di Mauro Giuseppe , Principi Nicola , Midulla Fabio , Esposito Susanna
Published: October 2024

Community-acquired pneumonia (CAP) is an acute infection of the lung parenchyma acquired outside the hospital or other healthcare settings, typically affecting previously healthy individuals. This intersociety consensus aims to provide evidence-based recommendations for the antibiotic treatment of mild to moderate CAP in previously healthy children in Italy.

A systematic review was conducted to identify the most recent and relevant evidence. Embase, Scopus, PubMed, and Cochrane databases were systematically screened, with a date restriction from 2012 to April 2024, but without language limitations. The review included studies conducted in high-income countries on antibiotic therapy in children over 3 months of age diagnosed with mild-moderate CAP. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods. The final recommendations were obtained through a Delphi consensus of an expert panel.

Amoxicillin is the first-line treatment if the child is at least immunized against Haemophilus influenzae type b (low/very low quality of evidence, strong recommendations), while amoxicillin-clavulanate or second- or third-generation cephalosporins should be prescribed for those unimmunized or with incomplete immunization coverage for both H. influenzae type b and Streptococcus pneumoniae (low/very low quality of evidence, strong recommendations). Macrolides should be considered in addition to amoxicillin in children over 5 years old, if symptoms persist and the clinical condition remains good after 48 h of therapy (low/very low quality of evidence, strong recommendations). The dosage of amoxicillin is 90 mg/kg/day divided in three doses, although two doses could be considered to improve compliance (moderate quality of evidence, weak recommendations). A five-day duration of therapy is recommended, with clinical monitoring and re-assessment approximately 72 h after the start of antibiotic treatment to evaluate symptom resolution (moderate quality of evidence, strong recommendations).

To improve the management of CAP in pediatric patients, we have developed this consensus based on a thorough review of the best available evidence and extensive discussions with an expert panel. However, further efforts are needed. Future research should focus on enhancing diagnostic accuracy, optimizing antibiotic utilization, comparing the efficacy of different antibiotic regimens, and determining the optimal dosage and duration of treatment in different setting.
Tranexamic Acid for reduction of intra- and postoperative TRansfusion requirements in elective Abdominal surgery (TATRA): study protocol for an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized superiority trial with two parallel groups
Authors: Ronellenfitsch Ulrich , Kestel Anita , Klose Johannes , Rebelo Artur , Bucher Michael , Ebert Daniel , Mikolajczyk Rafael , Wienke Andreas , Kegel Thomas , Hering Julian , Haiduk Christian , Richter Michael , Steighardt Jörg , Grohmann Erich , Otto Lutz , Kleeff Jörg
Published: October 2024

Background

Intra- and postoperative hemorrhage is a relevant problem in major abdominal surgery, leading to acute anemia and necessitating transfusion of packed red blood cells. It is estimated that in 30% of abdominal surgeries, intra- or postoperative transfusion is required. Transfusion potentially has detrimental health effects and poses a considerable socioeconomic burden. Tranexamic acid, a lysine analog inhibiting plasminogen activation and providing clot stability, has been used to reduce hemorrhage. While there is ample evidence in other surgical disciplines, it is almost completely lacking in abdominal surgery.

Methods

This multicenter double-blind parallel group randomized superiority trial will compare tranexamic acid (loading dose 1000 mg over 10 min prior to skin incision, maintenance dose 125 mg/h continuously until skin closure or until 1000 mg have been administered) to placebo in patients ≥ 18 years undergoing elective esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, or hepatectomy. The primary efficacy endpoint is the intra- or postoperative transfusion of at least one unit of packed red blood cells. Key secondary endpoints are the number of transfused units per patient, estimated intraoperative blood loss, postoperative complications/mortality, length of hospital stay, operation/anesthesia time, D-dimer levels, and quality of life. Sample size calculation is based on the assumption that in the control group, 30% of patients require transfusion while the intervention achieves a risk reduction of 33%, reducing the probability to 20%. With a type one error of 5% and a power of 90%, using a two-sided χ2 test, this results in 412 patients per group. Accounting for non-compliance, 425 patients are to be randomized per group. The total trial duration will be 30 months with a recruitment period of 18 months.

Discussion

If the proposed trial yielded positive results, the routine use of tranexamic acid in major abdominal surgery would be supported. This would avoid acute anemia with detrimental effects such as tissue hypoxia and organ injury, as well as the negative immediate and delayed effects of transfusions.

Trial registration

EU CT Nr: 2023–509970-43–01, NCT06414031. Registered on 10 May 2024.
Evaluating the efficacy of support groups in the metaverse for Ukrainian refugees: a protocol for a randomized clinical trial
Authors: Giosan Cezar , Popoviciu Cătălina-Maria , Zhamaliyeva Saltanat , Zaborot Iuliana , Deac George
Published: October 2024

Background

The Ukrainian crisis, sparked by the Russian invasion, has generated one of the most extensive refugee crises in modern history. Addressing the mental health challenges of Ukrainian refugees is critical to promoting their resilience and successful integration into host communities. Traditional support group interventions might be challenging to implement for geographically dispersed populations, making the metaverse an innovative and inclusive platform for providing much-needed support to such populations.

Methods/design

Displaced Ukrainian refugee adults (18 years or older) without current psychiatric diagnoses or current involvement in therapeutic interventions are included in the study. Participants are randomized to one of three conditions: (1) Metaverse Support Groups, (2) In-Person Support Groups, or (3) Waitlist. Both intervention groups (Metaverse and In-Person) undergo 5 support group sessions, and data are collected at baseline, mid-intervention, post-intervention, and 3-month follow-up. Primary outcomes are depressive symptomatology and anxiety. Secondary outcomes are perceived social support, well-being, and gender-based violence awareness.

Discussion

To our knowledge, this is the first attempt to test the efficacy of support groups in the Metaverse for the Ukrainian refugee population. This study can thus add substantially to the body of knowledge on effective interventions and policies for refugees.

Trial registration

ClinicalTrials.gov Identifier: NCT06142032 (https://clinicaltrials.gov/study/NCT06142032). Registered on November 8, 2023.
Reliability and validation of an electronic penicillin allergy risk-assessment tool in a pregnant population
Authors: Wang Joanne , Elwood Chelsea , Paquette Vanessa , Kwan Natasha , Erdle Stephanie , Watt Melissa , Van Schalkwyk Julie , Bone Jeffrey N. , Roberts Ashley , Mak Raymond , Wong Tiffany
Published: October 2024

Background

Penicillin allergy adversely impacts patient care, yet most cases do not have true allergies. Clinicians require efficient, reliable clinical tools to identify low risk patients who can be safely de-labeled. Our center implemented the FIRSTLINE electronic point-of-care decision support tool to help non-allergist practitioners risk stratify patients with penicillin allergy. We sought to explore the reliability and validity of this tool in relation to allergist assessment and actual patient outcomes. We additionally compared it with two other published stratification tools, JAMA and PENFAST, to assess ability to accurately identify low risk patients appropriate for direct oral challenge.

Methods

In this single-center, retrospective, observational study, 181 pregnant females with self-reported penicillin allergy between July 2019 to June 2021 at BC Women’s Hospital, Vancouver, Canada were used to assess the reliability and validity of all three tools. Physician-guided history of penicillin use and symptoms were used for scoring. Results and recommendations were compared to actual patient outcomes after clinician decision for direct oral challenge or intradermal tests. We compared the performance of JAMA, PENFAST and FIRSTLINE.

Results

181 patients were assessed. 176/181 (97.2%) patients were deemed not allergic. Each risk stratification tool labelled majority of patients as low risk with 88.4% of patients PENFAST 0–2, 60.2% of patients JAMA low risk, 86.7% of patients FIRSTLINE very low risk.

Conclusion

We demonstrate that our point-of-care electronic algorithm is reliable in identifying low risk pregnant patients, as compared to an allergist assessment. To our knowledge, this is the first study to provide direct comparison between multiple decision support tools using the same population, minimizing participant bias. Providing clinical algorithms to risk stratify patients, can enable healthcare professionals to safely identify individuals who may be candidates for direct penicillin oral challenges versus needing referral to specialists. This increases the generalizability and efficiency of penicillin allergy de-labeling.
Economic growth and unemployment nexus: empirical test of Okun’s law in Somalia
Authors: Mohamed Abdisalan Aden
Published: October 2024

This paper aims to empirically examine the relationship between GDP and unemployment in Somalia from 2000 to 2021. The study also estimates Okun's coefficient. To evaluate the association between the unemployment rate and economic growth, we employ the Hodrick–Prescott (HP) filter detrending technique, the Augmented Dickey–Fuller (ADF) test, ordinary least squares (OLS), and fully modified OLS. The findings of this study demonstrate that the series is stationary at the level. However, the results confirm a statistically insignificant negative relationship between unemployment and economic growth. Consequently, our findings suggest that Okun's law does not apply in Somalia. For robustness, we employ fully modified ordinary least squares (FMOLS), canonical cointegrating regression (CCR), and dynamic ordinary least squares (DOLS). Nevertheless, the relationship between the GDP gap and unemployment is not strong enough to be considered statistically significant, and other factors may also influence unemployment. Therefore, policies aimed at reducing unemployment should take into account various factors, including education and training, labor market regulations, and social protection measures.
Density of pure and mixed NaCl and CaCl2 aqueous solutions at 293 K to 353 K and 0.1 MPa: an integrated comparison of analytical and numerical data
Authors: Hoffert Ulrike , André Laurent , Blöcher Guido , Guignot Sylvain , Lassin Arnault , Milsch Harald , Sass Ingo
Published: October 2024

This study reports on newly acquired density data of synthetically prepared pure and mixed NaCl and CaCl2 aqueous solutions that span a wide range of geothermally encountered concentrations and mixing ratios. The analytical data are provided for the temperature range of 293–353 K at ambient pressure. For the reproduction of that data, PHREESCALE was used. The predictive potential of this numerical tool regarding the density of geothermal fluids of known composition was the major target herein. As a result, the measured data are in good agreement with previous analytical studies found in the literature. Possible sources of errors are discussed in this paper. Density data of the mixed solutions at temperatures other than ambient are unique and close existing data gaps. The numerical model reproduces the newly measured and already existing density data within an error band of approximately 1%. For further use in geothermal applications, this can be considered an excellent agreement. Moreover, the model yields a direct calculation of density without the need to establish complex empirical equations of state and mixing rules. Finally, sensitivity calculations performed with a thermal–hydraulic (TH) numerical reservoir model demonstrate the required accuracy of fluid density for reliably predicting the long-term performance of deep geothermal energy systems. In terms of the productivity index and the timing of thermal breakthrough it shows that the present analytical and numerical uncertainty in density is small enough to reliably state both reservoir parameters.
Research on wheel/rail contact surface temperature and damage characteristics during sliding contact of a wheel
Authors: Wei Yunpeng , Han Jihao , Yang Tao , Wu Yaping , Chen Zhidong
Published: October 2024

Severe friction on wheel/rail contact interface in the process of a train emergency braking can cause significant thermal and mechanical phenomena. Obvious friction heat and serious material damage will appear on the contact surface. In this article, the variation law of temperature and surface damage during a wheel sliding contact process are investigated. To achieve the research objective, a three-dimensional (3D) thermo-mechanical coupling contact finite element model (FEM) is established, and the temperature-dependent material parameters are used. The FEM is adopted to analyze the temperature distribution law on the contact surface. At the same time, a sliding contact testing machine is used to study the damage of materials in the contact area during the sliding contact. The study results indicate, the highest temperature of wheel and rail material is respectively 1014 ℃ and 461.8 ℃ during sliding contact. High temperatures are located at the subsurface and surface areas of contact region. When the distance to contact surface exceeds 1.4 mm, the temperature changes slightly. The types of damage on wheel surface are grooves and material peeling, while the flaky spalling, corrosive pitting, adhesion and grooves appear on the rail surface. Meanwhile, many cracks can be found on the contact surface, which is a major factor leading to material damage. The research results of this article are of great significance for understanding the thermal and mechanical damage of wheel/rail materials.
Early onset Colorectal Cancer and its association with its histological subtypes
Authors: Ibrar Fatima , Atiq Muslim , Farzana Shafqat  , Hadi Mohammad Khan
Published: October 2024

Objective: There are different clinicopathological features between early and late onset colorectal cancer. We aimed to characterize the histological features of colorectal cancer (CRC) at different age groups in our institution.
Methods: Total 232 patients with histologically proven colorectal cancer between ages 13-99 were included. This is retrospective study. Data collected from tumour registry Shifa International Hospital from January 1st 2018 to December 31st 2020. Pearson Chi square test was used for significance of categorical variables. P-values less than 0.05 were considered significant.
Results: Mean age at diagnosis was 55.49+/-16.43 years. Out of total 232 patients 58.6% were male and 41.3% were females (p value= 0.16). 150 (64.9%) were aged > 50 years and 81 (35.1%) were age < or equal to 50 years (p value = 0.44). Most common histological subtype was adenocarcinoma that was found in 188 (81%) cases. One hundred fifty five (66.8%) patients had Grade-II tumor, 67(28.9%) with Grade-III and 10 (4.3%) with Grade-I tumor. Fifty eight (25%) patients presented with metastatic disease. A significantly higher percentage of patients with signet ring cell cancer presented with a high-grade tumor when compared with patients with adenocarcinoma and mucinous carcinoma (93.7% vs 21.8%, p-value- <0.001%; 93.7% vs 39.2%, p-value <0.001).A significantly higher percentage of patients with mucinous adenocarcinoma and signet ring cell carcinoma presented at age less than 50 as compared to those with adenocarcinoma (60.7%, 56.2% and 30.8% respectively; p-value <0.05).
Conclusion: This study signifies that mucinous and signet ring cell type CRC present at an early age and with a higher proportion of patients with high tumour grade. Early diagnosis is key to help improve outcomes in these patients.
doi: https://doi.org/10.12669/pjms.40.10.10143
How to cite this: Ibrar F, Atiq M, Shafqat F, Khan HM. Early onset Colorectal Cancer and its association with its histological subtypes. Pak J Med Sci. 2024;40(10):2395-2399. doi: https://doi.org/10.12669/pjms.40.10.10143
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.
CRISPR Gene-Editing Combat: Targeting AIDS for total eradication
Authors: Nasrumminallah Maryam , Hadif Mohammad , Fatima Kashaf
Published: October 2024

doi: https://doi.org/10.12669/pjms.40.10.10257
How to cite this: Nasrumminallah M, Hadif M, Fatima K. CRISPR Gene-Editing Combat: Targeting AIDS for total eradication. Pak J Med Sci. 2024;40(10):2451. doi: https://doi.org/10.12669/pjms.40.10.10257
A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B
Authors: Wang Huan , Wu Liping
Published: October 2024

Objective: To compare the therapeutic efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients with chronic Hepatitis-B (CHB).
Methods: This retrospective study included 110 patients with CHB who received treatment at The First People’s Hospital of Linping District, Hangzhou from January 2021 to January 2023. Clinical data of the patients were reviewed and the patients were classified according to the treatment received: TDF group (n=53, patients received TDF treatment) and ETV group (n=57, patients received ETV treatment). Hepatitis-B virus deoxyribonucleic acid (HBV DNA) levels, liver function indicators, hepatitis-B e antigen (HBeAg) seroconversion rate, alanine transaminase (ALT) normalization rate, HBV DNA negative conversion rate, overall efficacy, and incidence of adverse reactions were compared.
Results: The total efficacy of the treatment in the TDF group was 94.33%, significantly higher than that in the ETV group (78.95%; P<0.05). After the treatment, the HBV DNA levels in both groups decreased compared to pretreatment levels, and were significantly lower in the TDF group compared to the ETV group (P<0.05). Both groups showed significant post-treatment improvement in liver function that was markedly better in the TDF group compared to the ETV group (P<0.05). The HBeAg seroconversion rate, ALT normalization rate, and HBV DNA conversion rate in the TDF group were significantly higher compared to the ETV group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups.
Conclusions: Compared with ETV, TDF has comparable adverse reaction profile but has more significant clinical effects in patients with CHB, improving HBeAg seroconversion rate, ALT normalization rate, and HBV DNA negative conversion rate. TDF is associated with lower HBV DNA levels after treatment and better improvements in liver function of patients.
doi: https://doi.org/10.12669/pjms.40.10.10307
How to cite this: Wang H, Wu L. A comparison of the therapeutic efficacy of Tenofovir Disoproxil Fumarate and Entecavir in patients with chronic Hepatitis-B. Pak J Med Sci. 2024;40(10):2390-2394. doi: https://doi.org/10.12669/pjms.40.10.10307
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.
Minimally invasive resection of a giant esophageal schwannoma
Authors: Sajida Qureshi  , Khan Sumayah , Abbasi Waqas Ahmad , Sohail Muneeba
Published: October 2024

Benign tumors of the esophagus are uncommon, and primary esophageal schwannoma of the esophagus is even rarer, accounting for 2% of cases. Less than 30 cases have been reported in the literature. Here we report a case of a young man with a symptomatic giant esophageal schwannoma, which was completely removed by laparoscopic three-staged esophagectomy. This is the first case of such a large lesion being removed by a minimally invasive approach. Our patient was a 22-year-old male, presented with dysphagia and dyspnea for five years. An endoscopy and CT scan suggested a giant leiomyoma. Postoperative biopsy revealed a primary esophageal schwannoma. We present our case of benign esophageal tumor measuring about 10.5 cm in greatest dimension. This is the first schwannoma resection performed with the Mckeown technique among the limited case reports in the literature. Esophageal schwannoma must be kept as a possible diagnosis in patients presenting with benign esophageal tumors. Esophagectomy is the mainstay of treatment for giant esophageal schwannomas. Minimally invasive esophagectomy can be safely performed for giant benign esophageal tumors.
doi: https://doi.org/10.12669/pjms.40.10.8824
How to cite this: Qureshi S, Khan S, Abbasi WA, Sohail M. Minimally invasive resection of a giant esophageal schwannoma. Pak J Med Sci. 2024;40(10):2447-2450. doi: https://doi.org/10.12669/pjms.40.10.8824
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.
Notes on the Siege’s Aftermath and Gendered Rhetoric in the Qur’an: Towards a Reconsideration of Q. 33:34
Authors: Geissinger Ash
Published: October 2024

This article re-examines a Qur’anic verse which has been largely overlooked in recent scholarship, 33:34a – wa-dhkurna mā yutlā fī buyūtikunna min āyāti llāhi wa l-ḥikma (remember what is recited in your houses of God’s revelations and wisdom). First, it provides an overview of the occasion-of-revelation traditions typically associated with the pericope within which this verse appears (Q. 33:28–34), and highlights several of this pericope’s unusual features which have yet to be convincingly accounted for. Then, the broader functions of gendered rhetoric in S. 33 (Sūrat al-Aḥzāb, “The Joint Forces”) are examined. Finally, it rereads the choice pericope with a focus on v. 34a, arguing that reading this verse as a command to the wives of Muḥammad to memorise his revelations or recite them to others coheres with the pericope and the broader themes of the sura. That there is likely a link between this verse and later traditions attributing various levels of involvement with the oral or written transmission of the Qur’anic text to several of the prophet’s wives is also asserted. This rereading both makes use of twenty-first-century approaches to research on the Qur’an through a gendered lens and further advances these, paying particular attention to how masculinity functions in the text, as well as to the relational nature of Qur’anic gender categories and their internal complexity.