bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Comparative Epigenetic Profiling Reveals Distinct Features of Mucosal Melanomas Associated with Immune Cell Infiltration and Their Clinical Implications
Authors: Dai Jie , Jia Jia , Zhang Fanshuang , Liu Kaihua , Xi Yanfeng , Yuan Pei , Mao Lili , Bai Xue , Wei Xiaoting , Wang Bingning , Li Jiangtao , Xu Yang , Liu Ting , Chang Shuang , Shao Yang , Guo Jun , Ying Jianming , Si Lu
Published: May 2024

Abstract
Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomic sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 patients with mucosal melanoma, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared with NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of patients with PMME and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T-cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.
Significance:
This study investigated the intricate epigenetic factor of mucosal melanomas contributed to the differential immune checkpoint inhibitor response, and found that PMME exhibited a global hypermethylation pattern and lower gene expression in comparison to NEMM. TERT hypermethylation may contribute to the favorable responses observed in patients with mucosal melanoma undergoing immunotherapy.
Fitwalking: A New Frontier for Kidney Patients. A Center' s Experience
Authors: Pozzato Marco , Parodi Giuseppe , Rossi Daniela , Stasi Elodie , Roccatello Dario
Published: May 2024

Background/Aims: Physical inactivity is common in patients with chronic kidney disease (CKD) and is an important modifiable risk factor for mortality, morbidity, and reduced quality of life. The present single-centre pilot study evaluated the possibility of performing structured physical exercise using a specific walking model, Fitwalking, in a population of patients with CKD and, according to the American College of Rheumatology guidelines, also in a population with immuno-rheumatological disease.
Methods: Patients were recruited from the nephrology, haemodialysis, peritoneal dialysis, transplantation, and immuno-rheumatology outpatient clinics. After general and functional clinical evaluation and exercise prescription at the Department of Sports Medicine, we performed scientifically proven tests on CKD (Six-minute walk test and Sit to stand test), before and after the Fitwalking technique training course, and again after 6 and 12 months, to evaluate its effectiveness and identify any critical issues.
Results: We enrolled 80 patients, (41 males, 51.2%), mean age 53±12 years; the clinical data showed statistically significant improvements in systolic, average, and differential blood pressure, average speed, and physical strength. Participants also adapted to muscle fatigue, experienced a reduction in BMI with stable lean mass and reduced fat mass, and reported improved perceptions of physical and mental health, and quality of life.
Conclusion: All enrolled patients successfully completed the process. A specific prescription was used that provided health education and allowed for the implementation of structured physical activity that could be performed safely and independently even after the training period. The activity was sustainable thanks to the training of in-house medical and nursing staff, demonstrating that it is possible to overcome this type of barrier to physical activity in CKD and in immuno-rheumatological patients.
Variants of Unknown Significance (VUS) in Maturity-Onset Diabetes of the Young (MODY): High Rate of Conundrum Resolution via VUS Reanalysis
Authors: Alarcon Guido , Maston Glenn A. , Hoffman Carol A. , Posey Jennifer E. , Redondo Maria Jose , Tosur Mustafa
Published: May 2024

Introduction:
In the era of next-generation sequencing, clinicians frequently encounter variants of unknown significance (VUS) in genetic testing. VUS may be reclassified overtime as genetic knowledge grows. We know little about how best to approach VUS in maturity-onset diabetes of the young (MODY). Therefore, our study aimed to determine the utility of reanalysis of previous VUS results in genetic confirmation of MODY.
Methods:
A single center retrospective chart review identified 85 subjects with a MODY clinical diagnosis. We reanalyzed genetic testing in 10 subjects with 14 unique VUS on MODY genes that was performed > 3 years before the study. Demographic, clinical, and biochemical data was collected for those individuals.
Results
After reanalysis, 43% (6/14) of the gene variants were reclassified to a different category: 7% (1/14) “likely pathogenic” and 36% (5/14) “benign” or “likely benign”. The reclassified pathogenic variant was in HNF1A and all reclassified benign variants were in HNF1A, HNF1B and PDX1. The median time between MODY testing and reclassification was 8 years (range: 4-10 years).
Conclusion:
In sum, iterative reanalyzing the genetic data from VUS found during MODY testing may provide high-yield diagnostic information. Further studies are warranted to identify the optimal time and frequency for such analyses.
valuation of different organic and inorganic fertilizer combinations on the growth and yield of cabbage
Authors: Aryal Dipak , Tamang Asmita , Gharti Magar Rishikesh
Published: May 2024

abbage (Brassica oleracea var. capitata) is the most important winter leafy vegetable in the world and belongs to the Cruciferae family. An experiment was conducted at the Horticultural farm of Gauradaha Agriculture Campus, Tribhuwan University, Jhapa, Nepal from 26th December 2022 to 2nd April 2023 to evaluate the different organic and inorganic fertilizer combinations on the growth and yield of cabbage (Brassica oleracea var. capitata L. cv. Green coronet). The experiment was conducted as a randomized block design with 7 treatments replicated 3 times and the treatments are T1: 25-ton FYM/ha, T2: 25-ton PM/ha, T3: 25-ton FYM/ha + NPK (RDF), T4: 25-ton PM/ha + NPK (RDF), T5: 20-ton FYM/ha + 10-ton PM/ha + NPK (RDF), T6: 10-ton FYM/ha + 20-ton PM/ha + NPK (RDF) and T7: control. Significant variation was found among the treatments. The result showed treatment had a significant role in different parameters. T3- The highest number of leaves, T5- the highest (leaf area, weight with roots, net head yield, horizontal head diameter), T4-highest (plant height, gross yield), T6- highest (stem girth, vertical head diameter) was obtained. On the result basis T5 (20-ton FYM/ha + 10-ton PM/ha + NPK (RDF) can be adopted as sustainable crop production. This study not only provides valuable insights into optimizing cabbage production but also underscores the importance of tailored fertilizer combinations for sustainable agriculture. Furthermore, the findings contribute to the broader discourse on enhancing crop yield while minimizing environmental impact. By elucidating the efficacy of specific fertilizer blends, this research paves the way for more efficient and eco-friendly farming practices, thereby promoting food security and environmental sustainability on a global scale.
Profe: te invito a jugar. El juego un espacio para la participación infantil
Authors: Mercedes Peña Ana , Marcela Castro Ángela
Published: May 2024

Desde un enfoque etnográfico y por medio de instrumentos como el diario de campo y la observación, es posible descubrir cómo la hora del descanso constituye para niños y niñas el momento más importante, permitiendo el encuentro con el otro, la diversión, la creatividad y hasta el conflicto; pero a su vez, reconoce un espacio donde los derechos políticos y civiles básicos, como el juego y la participación, aparecen desde ellos y ellas.

En esta investigación el papel que tienen niños y niñas con sus vivencias, expresiones, relaciones y juegos, desde la perspectiva etnográfica, hace posible recuperar sus voces, son ellos y ellas quienes por medio de sus expresiones, develan cómo viven y sienten la participación infantil desde el juego. Se retoman posturas de Trilla y Novella (2001) y Hart (1993) sobre participación infantil y de Huizinga (1972) en torno al juego.
Las representaciones sociales de la disciplina escolar. Ciclo IV de educación básica de la IED Orlando Fals Borda, localidad de Usme
Authors: Guillermo Rojas Luis , Acuña Germán
Published: May 2024

La comprensión de las representaciones sociales de la disciplina escolar, en docentes y estudiantes de ciclo IV de educación básica, através de la investigación realizada en una institución de educación pública de la ciudad de Bogotá, durante el segundo semestre de 2012, permite entender la disciplina como un fenómeno relacional que puede tomar matices que van desde el autoritarismo a la construcción de interacciones entre iguales, con consecuencias distintas para el ambiente escolar. La investigación se inscribe en la línea de: Educación y Pedagogías de la Alteridad, y se construye y desarrolla a partir de un diseño metodológico descriptivo interpretativo, en tanto toma en cuenta el contexto de la realidad cotidiana de los sujetos de estudio. Grados octavo y noveno de educación básica secundaria.
Narrativa corporal de sujetos sordos en resistencia al biopoder
Authors: Garay Porras Diana Xiomara
Published: May 2024

Este artículo presenta una reflexión en torno a los sentidos de resistencia al ideal de sujeto impuesto por las instituciones disciplinarias –familia, religión, hospital, escuela–, que construyen los sujetos sordos en narrativas visuales acerca de su experiencia corporal. Articula hallazgos de la investigación “Resignificar para re-existir: narrativas corporales de los sordos usuarios de lengua de señas colombiana, como prácticas de resistencia al biopoder”, realizada para optar al título de Magíster en Desarrollo Educativo y Social, en relación con las categorías de análisis: representación corporal, biotecnologías y construcción de subjetividades. El enfoque de la investigación es cualitativo-interpretativo y articula un diseño metodológico de construcción de historias de vida como terreno estratégico de trabajo. Finalmente, aborda una discusióndesde los saberes sometidos que emergen del colectivo sordo y se configuran apartir de una apuesta visual de un cuerpo intervenido, que resignifica sucondición biológica de sordera, para empoderar una condición social latente en escenarios de resistencia desde el discurso de las representaciones sociales. Aporta elementos de análisis frente a las prácticas institucionalizadas por saberes hegemónicos que han limitado la participación social con equidad y el reconocimiento de la diversidad lingüística y cultural de la comunidad sorda.
Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias
Authors: Weng Lu-Chen , Khurshid Shaan , Hall Amelia Weber , Nauffal Victor , Morrill Valerie N. , Sun Yan V. , Rämö Joel T. , Beer Dominik , Lee Simon , Nadkarni Girish , Johnson Renee , Andreasen Laura , Clayton Anne , Pullinger Clive R. , Yoneda Zachary T. , Friedman Daniel J. , Hyman Matthew C. , Judy Renae L. , Skanes Allan C. , Orland Kate M. , Jordà Paloma , Treu Timothy M. , Oetjens Matthew T. , Subbiah Rajesh , Hartmann Jacob P. , May Heidi T. , Kane John P. , Issa Tariq Z. , Nafissi Navid A. , Leong-Sit Peter , Dubé Marie-Pierre , Roselli Carolina , Choi Seung Hoan ,   FinnGen, Million Veteran Program, Regeneron Genetics Center, Tardif Jean-Claude , Khan Habib R. , Knight Stacey , Svendsen Jesper H. , Walker Bruce , Karlsson Linnér Richard , Gaziano J. Michael , Tadros Rafik , Fatkin Diane , Rader Daniel J. , Shah Svati H. , Roden Dan M. , Marcus Gregory M. , Loos Ruth J.F. , Damrauer Scott M. , Haggerty Christopher M. , Cho Kelly , Palotie Aarno , Olesen Morten S. , Eckhardt Lee L. , Roberts Jason D. , Cutler Michael J. , Shoemaker M. Benjamin , Wilson Peter W.F. , Ellinor Patrick T. , Lubitz Steven A.
Published: May 2024

BACKGROUND:

Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT).

METHODS:

We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies.

RESULTS:

Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate
NKX2-5
and
TTN
as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of
NKX2-5
and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate
SCN5A
,
SCN10A
, and
TTN/CCDC141
. Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals.

CONCLUSIONS:

Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.
Technical and Clinical Outcomes After Transcatheter Edge‐to‐Edge Repair of Mitral Regurgitation in Male and Female Patients: Is Equality Achieved?
Authors: Biasco Luigi , Tersalvi Gregorio , Klersy Catherine , Benfari Giovanni , Biaggi Patric , Corti Roberto , Curti Moreno , Gaemperli Oliver , Jeger Raban , Maisano Francesco , Mueller Olivier , Naegeli Barbara , Noble Stephane , Praz Fabien , Toggweiler Stefan , Valgimigli Marco , Cristoforetti Yvonne , Enriquez‐Sarano Maurice , Pedrazzini Giovanni
Published: May 2024

Background

Currently, no clear impact of sex on short‐ and long‐term survival following transcatheter edge‐to‐edge mitral valve repair (TEER) is evident, although no data are available on postprocedural life expectancy. Our aim was to assess sex‐specific differences in outcomes of patients with mitral regurgitation (MR) treated by TEER.

Methods and Results

Short‐term and 5‐year outcomes in men and women undergoing TEER between 2011 and 2018 who were included in the large, multicenter, real‐world MitraSwiss registry were analyzed. Outcomes were compared stratified by sex and according to MR cause (primary versus secondary). The impact of TEER on postprocedural life expectancy was estimated by relative survival analysis. Among 1142 patients aged 60 to 89 years, 39.8% were women. They were older, with fewer cardiovascular risk factors and lower functional capacity compared with men. Thirty‐day mortality was higher in men than in women (3.3% versus 1.1%; odds ratio, 3.16 [95% CI, 1.16–10.7];
P
=0.020). Five‐year survival was comparable in both sexes (adjusted hazard ratio for 5‐year mortality in men, 1.14 [95% CI, 0.90–1.44],
P
=0.275). Both men and women with either primary or secondary MR showed similar clinical efficacy over time. TEER provided high relative survival estimates among all groups, and fully restored predicted life expectancy in women with primary MR (5‐year relative survival estimate, 97.4% [95% CI, 85.5–107.0]).

Conclusions

TEER is not associated with increased short‐term mortality in women, whereas 5‐year outcomes are comparable between sexes. Moreover, TEER completely restored normal life expectancy in women with primary MR. A residual excess mortality persists in secondary MR, independently of sex.
Falsehood and False Prophets in Jeremiah
Authors: Koralija Srećko
Published: May 2024

This article explores the use of שֶׁקֶר in MT-Jer, and the manner in which the Septuagint (LXX) and Peshitta (P) read it. In that regard, the article also discusses lying, falsehoods (ψευδής, ψεῦδος, ἄδικος, µάτη, ܫܘܩܪܐ, ܕܓܠܘܬܐ), and false prophets (ψευδοπροφήτης, ܢܒܝܐ ܕܓܠܐ) in LXX and P. As such, it pioneers the examination of P-Jer’s perspective on false prophets. The article demonstrates that the translators of LXX and P approached the Hebrew source text in a manner that was not strictly literal, aligning with the nuances of the target language. It is argued that both LXX-Jer and P-Jer illuminate the polysemy inherent in the Hebrew lexeme שֶׁקֶר. In addition, both versions demonstrate a degree of textual liberty and interpretative renderings. Finally, the article demonstrates that unlike LXX, which labels Hananiah as a false prophet only once (LXX-Jer 35:1), P systematically designates him so throughout P-Jer 28. Consequently, the article also adds weight to the argument opposing a direct textual influence of LXX on P.
Can video streaming improve first aid for injured patients? A prospective observational study from Norway
Authors: Idland Siri , Kramer-Johansen Jo , Bakke Håkon Kvåle , Hagen Milada , Tønsager Kristin , Platou Hans-Christian Stoud , Hjortdahl Magnus
Published: May 2024

Background

Video streaming in emergency medical communication centers (EMCC) from caller to medical dispatcher has recently been introduced in some countries. Death by trauma is a leading cause of death and injuries are a frequent reason to contact EMCC. We aimed to investigate if video streaming is associated with recognition of a need for first aid during calls regarding injured patients and improve quality of bystander first aid.

Methods

A prospective observational study including patients from three health regions in Norway, from November 2021 to February 2023 (registered in clinical trials 10/25/2021, NCT05121649). Cases where video streaming had been used as a supplement during the medical emergency call were compared to cases where video streaming was not used during the call. Patients were included by ambulance personnel on the scene of accident if they met the following criteria: 1. Ambulance personnel arrived at a patient who had an injury, 2. One or more bystanders had been present before their arrival, 3. One or more of the following first aid measures had been performed by bystander or should have been performed: airway management, control of external bleeding, recovery position, and hypothermia prevention. Ambulance personnel assessed quality of first aid performed by bystander, and information concerning use of video streaming and patient need for first aid measures recognized by dispatcher was collected through EMCC audio logs and patient charts. We present descriptive data and results from a logistic regression analysis.

Results

Data was collected on 113 cases, and dispatchers used video streaming in addition to standard telephone communication in 12/113 (10%) of the cases. The odds for the dispatcher to recognize a need for first aid during a medical emergency call were more than five times higher when video streaming was used compared to no use of video streaming (OR 5.30, 95% CI 1.11-25.44). Overall quality of bystander first aid was rated as “high”. The odds ratio for the patient receiving first aid of higher quality were 1.82 (p-value 0.46) when video streaming was used by dispatcher during the call.

Conclusion

Our findings show that video streaming is not frequently used by dispatchers in calls regarding patients with injuries, but that video streaming is associated with improved recognition of patients’ first aid needs. We found no statistically significant difference in first aid quality comparing the calls where video streaming as a supplement were used with the calls with audio only.
Safety profiles of offspring born from early-follicular long-acting GnRH agonist protocol and daily mid-luteal GnRH agonist protocol: a retrospective study
Authors: Du Linqing , Song Jianyuan , Fan Wenqian , Ye Tian , Kong Huijuan
Published: May 2024

Background

The gonadotropin hormone-releasing hormone agonists (GnRH-a) have been widely used for controlled ovarian stimulation in assisted reproductive technology (ART). The early-follicular long-acting GnRH-a long protocol (EFL) and the luteal phase short-acting GnRH-a long protocol (LPS) are commonly used GnRH agonist protocols. We conducted a retrospective analysis to assess and compare the rates of congenital abnormalities and safety profiles in offspring born from the EFL and LPS protocols.

Methods

We conducted a retrospective cohort study to analyze and compare neonatal data from patients who using EFL or LPS protocols at our center between January 1, 2014, and June 30, 2017. The study ultimately included 1810 neonates from 1401 cycles using the EFL protocol and 2700 neonates from 2129 cycles using the LPS protocol.The main outcome measures are gestational age at delivery, birth weight, and congenital anomaly rate.To assess the influence of various factors on congenital abnormalities, a random-effects logistic regression model was employed.

Results

The EFL and LPS protocols led to similar congenital anomaly rates (1.64% vs. 2.35%, P = 0.149). No significant differences were found between the two groups regarding birth weight and its categories, newborn gender and congenital anomaly rate. The results of the multivariate logistic regression model indicated no association between congenital anomaly and BMI, duration of infertility, treatment protocol, fertilization method, or embryo transfer stage. Compared with singleton pregnancies, the probability of congenital defects in multiple pregnancies was 2.64 times higher (OR: 2.64, 95% CI: 1.72–4.05, P < 0.0001). Newborns with congenital defects were born with a lower gestational age compared with full-term pregnancies.

Conclusion

In conclusion, the EFL protocol is considered a safe option for ensuring offspring safety, comparable with the LPS protocol; however, multiple pregnancies represent an independent risk factor for congenital abnormalities. This approach can be widely adopted; however, prioritizing single embryo transfers is strongly recommended to minimize the potential risks associated with multiple pregnancies in offspring.
Bilateral optic nerve infiltration and leukemic retinopathy as initial signs of leukemia relapse with central nervous system involvement in an adult: a case report
Authors: Wang Yisai , Zhu Ling , Wang Hongtao , Li Zhen , Bai Ruomeng , Wei Qinghua , Huang Lin , Xu Ying , Li Songguo , Chen Hui
Published: May 2024

Background

We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement.

Case presentation

A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased.

Conclusions

To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.
Existing psychological supportive care interventions for cervical cancer patients: a systematic review and meta-analysis
Authors: Dhakal Kamala , Chen Changying , Wang Panpan , Mboineki Joanes Faustine , Adhikari Bibhav
Published: May 2024

Cervical cancer patients commonly experience psychological supportive care needs, necessitating diverse interventions to enhance psychological well-being and alleviate physical symptoms. This systematic review, covering English-published articles from January 1999 to April 2023, assessed the impact of psychological supportive care interventions on anxiety and depression. Twenty-Six studies, including 11,638 patients, were analyzed, comprising randomized controlled trials; quasi-experimental, and pre-post-test designs from PubMed; Science Direct; Wiley online library; Google Scholar; Cochrane Library; and JSTOR. The extraction of data was done by two independent authors and a third independent author checked the data extraction. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 2020 statement was adopted. The population, intervention, comparator, and outcomes (PICO) search strategy was applied. Effective Public Health Practice Project (EPHPP) tool was used to assess the quality of selected articles. Various interventions, such as psychological nursing, exercise, counselling, psycho-curative approaches, peer and family education, psychotherapy, and medication, were identified. Two studies incorporated homework sessions, predominantly administered by nursing staff. Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were commonly used instruments. Statistical analysis revealed a significant difference in anxiety and depression scores between treatment and control groups (p < 0.005) post-intervention across all studies. A subsequent meta-analysis of eight homogeneous studies, utilizing a random-effects model, showed a moderate-to-high overall effect size (1.35, 95% CI: 0.75 to 1.94), indicating a statistically significant positive impact. Various studies exhibited variability in effect sizes ranging from low to high. While the meta-analysis included 936 participants, the forest plot visually represents individual study effect sizes and the combined effect size. Preliminary evidence supports the positive impact of psychological supportive care interventions on cervical cancer outcomes, urging further research, especially exploring long-term effects and employing rigorous study designs.
Utilizing disease transmission and response capacities to optimize covid-19 control in Malaysia
Authors: Singh Sarbhan , Herng Lai Chee , Iderus Nuur Hafizah Md. , Ghazali Sumarni Mohd , Ahmad Lonny Chen Rong Qi , Ghazali Nur’ain Mohd , Nadzri Mohd Nadzmi Md , Anuar Asrul , Kamarudin Mohd Kamarulariffin , Cheng Lim Mei , Tee Kok Keng , Lin Chong Zhuo , Gill Balvinder Singh , Ahmad Nur Ar Rabiah Binti
Published: May 2024

Objectives

Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia.

Methods

Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed.

Results

CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p < 0.001] with the COVID-19 cases. The estimated SL was strongly correlated with COVID-19 cases (ρ = 0.845, p < 0.001) and responded well to the various COVID-19 case trends during the pandemic. SL changes occurred earlier during the increase of cases but slower during the decrease, indicating a conservative response. The automated web-based system developed produced daily real-time CT, RC, and SL for the COVID-19 pandemic.

Conclusions

The indicators selected and combinations formed were able to generate validated daily CT and RC levels for Malaysia. Subsequently, the CT and RC levels were able to provide accurate and sensitive information for the estimation of SL which provided valuable evidence on the progression of the pandemic and movement restriction adjustment for the control of Malaysia.
Hip biomechanics in patients with low back pain, what do we know? A systematic review
Authors: Pizol Gustavo Zanotti , Miyamoto Gisela Cristiane , Cabral Cristina Maria Nunes
Published: May 2024

Background

Biomechanical alterations in patients with low back pain (LBP), as reduced range of motion or strength, do not appear to be exclusively related to the trunk. Thus, studies have investigated biomechanical changes in the hip, due to the proximity of this joint to the low back region. However, the relationship between hip biomechanical changes in patients with LBP is still controversial and needs to be summarized. Therefore, the aim of this study was to systematically review observational studies that used biomechanical assessments in patients with non-specific LBP.

Methods

The search for observational studies that evaluated hip biomechanical variables (i.e., range of motion, kinematic, strength, and electromyography) in adults with non-specific acute, subacute, and chronic LBP was performed in the PubMed, Embase, Cinahl and Sportdiscus databases on February 22nd, 2024. Four blocks of descriptors were used: 1) type of study, 2) LBP, 3) hip and 4) biomechanical assessment. Two independent assessors selected eligible studies and extracted the following data: author, year of publication, country, study objective, participant characteristics, outcomes, and results. The methodological quality of the studies was assessed using the Epidemiological Appraisal Instrument and classified as low, moderate, and high. Due to the heterogeneity of the biomechanical assessment and, consequently, of the results among eligible studies, a descriptive analysis was performed.

Results

The search strategy returned 338 articles of which 54 were included: nine articles evaluating range of motion, 16 evaluating kinematic, four strength, seven electromyography and 18 evaluating more than one outcome. The studies presented moderate and high methodological quality. Patients with LBP, regardless of symptoms, showed a significant reduction in hip range of motion, especially hip internal rotation, reduction in the time to perform functional activities such as sit-to-stance-to-sit, sit-to-stand or walking, greater activation of the hamstrings and gluteus maximus muscles and weakness of the hip abductor and extensor muscles during specific tests and functional activities compared to healthy individuals.

Conclusion

Patients with LBP present changes in range of motion, task execution, activation, and hip muscle strength when compared to healthy individuals. Therefore, clinicians must pay greater attention to the assessment and management of the hip during the treatment of these patients.

Systematic review registration

International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020213599).
Immediate implant placement influenced by musical flow: a prospective randomized controlled clinical trial
Authors: Pellicer Lorenzo Esteban , Rubio José Luis Martínez , Casañas Elisabeth , Villar Antonio Conde
Published: May 2024

Background

The purpose of this study was to test how musical flow using baroque (BM) and classical era music (CM) as a non-pharmacological therapy can control anxiety and pain levels among patients undergoing IPI (Immediate post-extraction implants).

Methods

78 patients who required an IPI were enrolled in this randomized clinical trial. Each patient was assigned to one of the three experimental groups with a simple randomization: Group I (n = 26) listened to BM; Group II (n = 27) listened to CM; and Group III (n = 25) did not listen to music and was the control group (C). The physiological dependent variables analyzed were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and oxygen saturation (SpO2). The psychological dependent variable analyzed was modified dental anxiety scale (MDAS) and visual analogue scale (VAS), measured before and after surgery. In all cases, the level of statistical significance was set at p < 0.01.

Results

Statistically significant differences were found in the SBP decrease in the CM group (p = 0.001, CI = 1.9716–6.5840) and the BM group (p = 0.003, CI = 1.4450–6.4396). Anxiety levels during the intervention decreased in both groups that listened to music: BM group (p = 0.002, CI = 0.645–2.662) and CM group (p = 0.000, CI = 1.523–3.884).

Conclusions

Patients undergoing IPI placement surgery can register lower levels of SBP when listening to BM and CM than patients who were not exposed to the musical flow, improving their anxiety levels.
Effect of cevimeline and different concentration of gum arabic on parotid salivary gland function in methotrexate-induced xerostomia: a comparative study
Authors: Aboulfotoh Mahmoud Mohamed
Published: May 2024

Objective

This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate.

Methods

One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups received a 10% W/V aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey’s multiple comparisons post hoc test.

Results

Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively.

Conclusion

GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.
Adapting to new challenges in medical education: a three-step digitization approach for blended learning
Authors: Gellisch Morris , Morosan-Puopolo Gabriela , Brand-Saberi Beate , Schäfer Thorsten
Published: May 2024

This research work focuses on evaluating the development of our three-step digitization approach, designed to transform traditional lectures into engaging digital learning experiences. Aimed at offering an easy-to-use solution for educators, this approach addresses the pressing challenges of modern educational environments by enhancing accessibility, engagement, and effectiveness of learning through digital means.

Quantitative analysis demonstrated a notable increase in knowledge gain for students engaged with the digital format (t(230) = -2.795, p = 0.006) over traditional methods. Additionally, it was observed that the online setting significantly improved concentration levels (t(230) = -5.801, p < .001) and reduced distractions (t(230) = 2.848, p = 0.005). Emotional assessments, based on the Achievement Emotions Questionnaire (AEQ), indicated an elevation in enjoyment (t(230) = -4.717, p < .001) and a reduction in anxiety (t(230) = 9.446, p < .001) within the digital learning environment. A substantial preference for the digital course format was expressed by 61.0% of participants, with 71.4% acknowledging its superior efficiency compared to 14.3% for traditional lectures.

Qualitative feedback underscored the digital format's flexibility, comprehensive learning experience, and immediate feedback as key benefits. Nevertheless, nuances such as a preferred understanding in face-to-face interactions and the absence of a social component in digital settings were noted.

To conclude, the findings from this study illuminate the significant advantages of the three-step digitization approach in meeting contemporary educational challenges. By facilitating an enhanced knowledge acquisition and fostering a supportive emotional climate, this approach signifies a promising direction for the future of medical education and beyond, fusing the convenience of digital solutions with the depth and engagement of traditional learning methodologies.
Virtual reality simulation training in laparoscopic surgery – does it really matter, what simulator to use? Results of a cross-sectional study
Authors: Sparn Moritz B. , Teixeira Hugo , Chatziisaak Dimitrios , Schmied Bruno , Hahnloser Dieter , Bischofberger Stephan
Published: May 2024

Background

Virtual reality simulation training plays a crucial role in modern surgical training, as it facilitates trainees to carry out surgical procedures or parts of it without the need for training “on the patient”. However, there are no data comparing different commercially available high-end virtual reality simulators.

Methods

Trainees of an international gastrointestinal surgery workshop practiced in different sequences on LaparoS® (VirtaMed), LapSim® (Surgical Science) and LapMentor III® (Simbionix) eight comparable exercises, training the same basic laparoscopic skills. Simulator based metrics were compared between an entrance and exit examination.

Results

All trainees significantly improved their basic laparoscopic skills performance, regardless of the sequence in which they used the three simulators. Median path length was initially 830 cm and 463 cm on the exit examination (p < 0.001), median time taken improved from 305 to 167 s (p < 0.001).

Conclusions

All Simulators trained efficiently the same basic surgery skills, regardless of the sequence or simulator used. Virtual reality simulation training, regardless of the simulator used, should be incorporated in all surgical training programs. To enhance comparability across different types of simulators, standardized outcome metrics should be implemented.
Leadership in intellectual disability practice: design, development, and evaluation of a programme to support practice
Authors: Doody Owen , O’Halloran Maeve , Carey Eileen , Kilduff Marie , Gilmartin Ann , Ryan Ruth
Published: May 2024

Background

Intellectual disability services have and continue to experience changes in service provision. This has an implication for leadership in practice as the quality of leadership has a direct influence on staff practice and care provided.

Aim

To design, deliver, and evaluate a leadership programme for nurse and social care managers in Ireland.

Design

An accredited programme was designed based on evidence from literature, practice, and national expertise. A cross-sectional survey was used to collect information on the attitudes and behaviour of participants before commencing and after completing the programme. Data from the questionnaires were analysed using SPSS and open-ended questions were analysed using content analysis.

Setting

Intellectual disability services.

Participants

102 participants completed the programme and survey.

Methods

Pre-post survey and reported using the CROSS guidelines.

Results

Participants’ expectations were rated highly, and all items scored higher in the post-survey. Qualitative data was overall positive regarding opportunities for more time to work through each aspect of the programme. The key learning was through the forum day where participants shared their group projects.

Conclusions

Overall, the programme was positively evaluated and through engaging with the programme participants’ perceptions moved from seeing leadership as mostly task-oriented to realising that qualities such as good communication, person-centredness, advocacy, supporting, role modelling, and empowering are key to leadership.
Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort
Authors: Matta Komodo , Viallon Vivian , Botteri Edoardo , Peveri Giulia , Dahm Christina , Nannsen Anne Østergaard , Olsen Anja , Tjønneland Anne , Elbaz Alexis , Artaud Fanny , Marques Chloé , Kaaks Rudolf , Katzke Verena , Schulze Matthias B. , Llanaj Erand , Masala Giovanna , Pala Valeria , Panico Salvatore , Tumino Rosario , Ricceri Fulvio , Derksen Jeroen W. G. , Nøst Therese Haugdahl , Sandanger Torkjel M. , Borch Kristin Benjaminsen , Quirós J. Ramón , Castro-Espin Carlota , Sánchez Maria-José , Atxega Amaia Aizpurua , Cirera Lluís , Guevara Marcela , Manjer Jonas , Tin Tin Sandar , Heath Alicia , Touvier Mathilde , Goldberg Marcel , Weiderpass Elisabete , Gunter Marc J. , Freisling Heinz , Riboli Elio , Ferrari Pietro
Published: May 2024

Background

Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality.

Methods

Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35–70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years).

Results

After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI.

Conclusions

Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.
The efficacy and safety of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, in patients with advanced head and neck mucosal melanoma harboring CDK4 amplification
Authors: Shi Chaoji , Ju Houyu , Zhou Rong , Xu Shengming , Wu Yunteng , Gu Ziyue , Wang Ying , Chen Wanling , Huang Xinyi , Han Yong , Sun Shuyang , Li Chuwen , Wang Min , Zhou Guoyu , Zhang Zhiyuan , Li Jiang , Ren Guoxin
Published: May 2024

Background

Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification.

Methods

The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494–0.957) and 51.6% (95% CI, 0.307–0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue.

Conclusions

Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration.

Trial registration

ChiCTR2000031608.