bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials
Authors: Abbas Abdallah , Fayoud Aya M , El Din Moawad Mostafa Hossam , Hamad Abdullah Ashraf , Hamouda Heba , Fouad Eman A. 
Published: March 2024

Abstract
Introduction
Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions.

Objective
To evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients.

Methods
We identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion. Two independent reviewers evaluated the identified studies’ titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome, we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3.

Results
Among the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200 mg dosage (overall mean difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200 mg dosage (overall mean difference: -0.34, p < 0.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200 mg), vomiting (200 mg), and irritability (200 mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite.

Conclusion
Trofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200 mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.
Risk factors of necrotizing enterocolitis in twin preterm infants
Authors: Xie Ying-Ling , Lai Shu-Hua , Liu Su-Jia , Xiu Wen-Long 
Published: March 2024

Abstract
Purpose
This study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants.

Methods
The clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not.

Results
Univariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P < 0.05).

Conclusion
Occurrence of NEC was associated with congenital heart disease, small for gestational age, and asphyxia at birth. For twin preterm infants with congenital heart disease, small for gestational age, or asphyxia at birth, special attention should be paid to the occurrence of NEC to minimize and avoid the occurrence of NEC.
Efficacy and mechanisms of cannabis oil for alleviating side effects of breast cancer chemotherapy (CBC2): protocol for randomized controlled trial
Authors: Thu May Soe , Pongpirul Krit , Vongsaisuwon Mawin , Vinayanuwattikun Chanida , Banchuen Kamonwan , Ondee Thunnicha , Payungporn Sunchai , Phutrakool Phanupong , Nootim Preecha , Chariyavilaskul Pajaree , Cherdchom Sarocha , Wanaratna Kulthanit , Hirankarn Nattiya 
Published: March 2024

Abstract
Background
In a pilot study using both cannabidiol (CBD) and tetrahydrocannabinol (THC) as single agents in advanced cancer patients undergoing palliative care in Thailand, the doses were generally well tolerated, and the outcome measure of total symptom distress scores showed overall symptom benefit. The current study aims to determine the intensity of the symptoms experienced by breast cancer patients, to explore the microbiome profile, cytokines, and bacterial metabolites before and after the treatment with cannabis oil or no cannabis oil, and to study the pharmacokinetics parameters and pharmacogenetics profile of the doses.

Methods
A randomized, double-blinded, placebo-controlled trial will be conducted on the breast cancer cases who were diagnosed with breast cancer and currently receiving chemotherapy at King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand. Block randomization will be used to allocate the patients into three groups: Ganja Oil (THC 2 mg/ml; THC 0.08 mg/drop, and CBD 0.02 mg/drop), Metta Osot (THC 81 mg/ml; THC 3 mg/drop), and placebo oil. The Edmonton Symptom Assessment System (ESAS), Food Frequency Questionnaires (FFQ), microbiome profile, cytokines, and bacterial metabolites will be assessed before and after the interventions, along with pharmacokinetic and pharmacogenetic profile of the treatment during the intervention.

Trial registration
TCTR20220809001.
Developing an innovative national ACP-OSCE program in Taiwan: a mixed method study
Authors: Wu Yen-Lin , Hsieh Tsu-Yi , Hwang Sheau-Feng , Lin Yi-Yin , Chu Wei-Min 
Published: March 2024

AbstractObjectivesTo evaluate the process and the comprehensiveness of advance care planning (ACP), we designed a national ACP-OSCE (Objective Structured Clinical Examination) program.MethodsThe program was designed as a 40-minute OSCE test. Participants were categorized as different ACP team members to illustrate realistic scenarios. Preceptors were asked to observe ACP professionals’ actions, responses, and communication skills during ACP with standardized patients (SP) through a one-way mirror. Participants’ communication skills, medical expertise, legal knowledge, empathetic response and problem-solving skills of ACP were also self-evaluated before and after OSCE. Thematic analysis was used for qualitative analysis.ResultsIn Nov 2019, a total of 18 ACP teams with 38 ACP professionals completed the ACP-OSCE program, including 15 physicians, 15 nurses, 5 social workers, and 3 psychologists. After the ACP-OSCE program, the average score of communication skills, medical expertise, legal knowledge, empathetic response, ACP problem-solving all increased. Nurses felt improved in medical expertise, legal knowledge, and problem-solving skills, psychologists and social workers felt improved in legal knowledge, while physicians felt no improved in all domain, statistically. Thematic analysis showed professional skills, doctoral-patient communication, benefit and difficulties of ACP were the topics which participants care about. Meanwhile, most participants agreed that ACP-OSCE program is an appropriate educational tool.ConclusionThis is the first national ACP-OSCE program in Asia. We believe that this ACP-OSCE program could be applied in other countries to improve the ACP process and quality.
Increased di-(2-ethylhexyl) phthalate exposure poses a differential risk for adult asthma clusters
Authors: Hsu Yuan-Ting , Wu Chao-Chien , Wang Chin-Chou , Sheu Chau-Chyun , Yang Yi-Hsin , Cheng Ming-Yen , Lai Ruay-Sheng , Leung Sum-Yee , Lin Chi-Cheng , Wei Yu-Feng , Lai Yung-Fa , Cheng Meng-Hsuan , Chen Huang-Chi , Yang Chih-Jen , Wang Chien-Jen , Liu Huei-Ju , Chen Hua-Ling , Hung Chih-Hsing , Lee Chon-Lin , Huang Ming-Shyan , Huang Shau-Ku 
Published: March 2024

Abstract
Background
DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are “non-atopic”, lacking a clear etiology.

Methods
In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman’s rank correlation coefficients, multiple logistic regression, and multinomial logistic regression.

Results
Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified.

Conclusion
The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies.
Residents’ experiences during a hydrogen sulfide crisis in Carson, California
Authors: Quist Arbor J. L. , Hovav April , Silverman Alexander D. , Shamasunder Bhavna , Johnston Jill E. 
Published: March 2024

Abstract
Background
In early October 2021, thousands of residents in Carson, California began complaining of malodors and headaches. Hydrogen sulfide (H2S), a noxious odorous gas, was measured at concentrations up to 7000 parts per billion (ppb) and remained above California’s acute air quality standard of 30 ppb for a month. Intermittent elevations of H2S continued for 3 months. After 2 months of malodor in this environmental justice community, a government agency attributed the H2S to environmental pollution from a warehouse fire. Research has yielded conflicting results on the health effects of H2S exposure at levels that were experienced during this event. This research fills a critical need for understanding how people perceive and experience emergent environmental health events and will help shape future responses.

Methods
Through a community-academic partnership, we conducted 6 focus groups with 33 participants who resided in the Carson area during the crisis. We sought to understand how this incident affected residents through facilitated discussion on topics including information acquisition, impressions of the emergency response, health symptoms, and ongoing impacts.

Results
The majority of participants were women (n = 25), identified as Latina/o (n = 19), and rent their homes (n = 21). Participants described difficulty obtaining coherent information about the emergency, which resulted in feelings of abandonment. Most participants felt that local government and healthcare providers downplayed and/or disregarded their concerns despite ongoing odors and health symptoms. Participants described experiencing stress from the odors’ unknown health effects and continued fear of future odor incidents. Residents sought to take control of the crisis through information sharing, community networking, and activism. Participants experienced longer term effects from this event, including increased awareness of pollution and reduced trust in local agencies.

Discussion
This study demonstrates the necessity of clear, comprehensive, and prompt responses by relevant decisionmakers to chemical emergencies to appropriately address residents’ fears, curb the spread of misinformation, and minimize adverse health effects. Participant responses also point to the benefit of supporting horizontal community networks for improved information sharing. By engaging directly with community members, researchers and disaster responders can better understand the various and complex impacts of chemical disasters and can improve response.
Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis
Authors: Li Jiao , Wang Fei , Li Zhen , Feng Jingjing , Men Yi , Han Jinming , Xia Jiangwei , Zhang Chen , Han Yilai , Chen Teng , Zhao Yinan , Zhou Sirui , Da Yuwei , Chai Guoliang , Hao Junwei 
Published: March 2024

Abstract
Background
Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG.

Methods
By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk.

Results
We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk.

Conclusions
This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.
Botulinum toxin: a new differential diagnosis for a lytic bone lesion
Authors: Lefkovits Yael , Lipton Lara 
Published: March 2024

Abstract
Background
Botulinum toxin, produced by the Gram-positive anaerobe Clostridium botulinum, is composed of seven antigenic subtypes (A, B, C, D, E, F, and G). Currently, only Botulinum toxin type A, commonly referred to as “Botox,” is approved for clinical use, given its relatively safe clinical profile. Botulinum toxin type A has a wide range of therapeutic indications, including treatment for dystonia, migraine headache, neurogenic bladder, and large muscle spastic disorders. However, the toxin is most widely known for its cosmetic effects in treating wrinkles and facial lines.

Case presentation
This article describes a 62-year-old Caucasian female who presented for investigation and workup of an isolated lytic lesion of her frontal bone a few weeks after administration of botulinum toxin injection into the corresponding site in the frontalis muscle. This presented as a large, palpable, painless forehead lump causing significant psychological distress. After no neoplastic cause for the lesion was found and histopathology was performed, our researchers concluded that the most likely explanation was that the bony lytic lesion resulted from inadvertent injection of the “Botox” neurotoxin through the intended target muscle and into the cortex of the underlying bone.

Conclusions
Our search of the literature failed to identify any previous cases of this occurring. However, as the popularity of this cosmetic procedure only increases, we believe that this represents an important possible differential for isolated lytic lesion after administration of “Botox” injection.
Stigma, depression, and quality of life among people with pulmonary tuberculosis diagnosed through active and passive case finding in Nepal: a prospective cohort study
Authors: Dixit Kritika , Rai Bhola , Aryal Tara Prasad , de Siqueira-Filha Noemia Teixeira , Dhital Raghu , Sah Manoj Kumar , Pandit Ram Narayan , Majhi Govinda , Paudel Puskar Raj , Levy Jens W. , van Rest Job , Gurung Suman Chandra , Mishra Gokul , Lönnroth Knut , Squire Stephen Bertel , Annerstedt Kristi Sidney , Bonnett Laura , Fuady Ahmad , Caws Maxine , Wingfield Tom 
Published: March 2024

Abstract
Background
The psychosocial consequences of tuberculosis (TB) are key barriers to ending TB globally. We evaluated and compared stigma, depression, and quality of life (QoL) among people with TB diagnosed through active (ACF) and passive (PCF) case-finding in Nepal.

Methods
We prospectively recruited adults with TB diagnosed through ACF and PCF in four districts of Nepal between August 2018 and April 2019. Participants were interviewed at 8–12 weeks (baseline) and 22–26 weeks (follow-up) following treatment initiation. TB stigma was measured using an adapted Van Rie Stigma Scale (0 = no stigma to 30 = highest stigma). Depression was measured using a locally-validated Patient Health Questionnaire (PHQ-9). Mild and major depression were indicated by PHQ-9 scores 5–9 and ≥ 10, respectively. QoL was measured using the EuroQoL 5-Dimension 5-level (EQ-5D-5L) from 0 to 1 (optimal QoL); and self-rated health from 0 to 100 (optimal self-rated health).

Results
We recruited 221 participants (111 ACF; 110 PCF) with a mean age of 48 years (standard deviation [SD] =  ± 16), of whom 147/221 (67%) were men. The mean TB stigma score was 12 (SD = 7.3) at baseline and 12 (SD = 6.7) at follow-up. The most commonly perceived elements of TB stigma at baseline were that people with TB experienced guilt (110/221, 50%) and feared disclosure outside their household (114/221, 52%). Self-rated health and EQ-5D-5L scores increased from baseline to follow-up (69.3 to 80.3, p < 0.001; 0.92 to 0.9, p = 0.009). Nearly one-third of participants (68/221, 31%) had mild or major depression at baseline. The proportion of participants with major depression decreased from baseline to follow-up (11.5% vs. 5%, p = 0.012). There was a moderate, significant positive correlation between depression and stigma scores (r = 0.41, p < 0.001). There were no differences found in TB stigma, self-rated health, QoL, or prevalence of mild/major depression between ACF and PCF participants.

Conclusions
We found a substantial, persistent, and clustered psychosocial impact among adults with TB diagnosed through both ACF and PCF strategies in Nepal. These findings suggest an urgent need to develop effective, evidence-based psychosocial support interventions with the potential to be integrated with existing ACF strategies and routine TB service activities.
Auditives Dekodierungstraining zur Unterstützung der Dolmetscherausbildung: Die Rolle der deutschen Sprachvarietäten und der neuen Technologien
Authors: Morf Miriam 
Published: March 2024

The paper aims to propose a reflection on the importance of German varieties in the preparation of interpreters. Like many other languages, German is classified as a pluricentric language, i. e. a language officially spoken in more than one centre or nation. This makes it a very variegated language that boasts a multitude of both standard and non-standard varieties. The task of interpreters who choose German as a foreign language is therefore to be able to understand and translate into another language what is spoken by native speakers of German, many of whom, according to the previous statement, often speak different varieties. To do this, the interpreters’ preparation must consider the inclusion of the different language varieties of both standard and non-standard German, especially at the level of auditory decoding, in order to facilitate the understanding of the message at a receptive level. Starting from the definition of a pluricentric language, this contribution will highlight the main difficulties of interpreters at the level of listening comprehension, most of which are found at the level of auditory decoding, before proposing training aimed at decoding the different varieties of standard and non-standard German realised through the use of new technologies.
Estudio del efecto del tratamiento con fármacos antidiabéticos sobre el metabolismo óseo
Authors: Padilla Apuntate Nuria , Puerto Cabeza Carmen G. , Gallego Royo Alba , Goñi Ros Nuria , Abadía Molina Claudia , Acha Pérez Javier , Calmarza Pilar 
Published: March 2024

Resumen

Objetivos
La prevalencia de la diabetes mellitus tipo 2 (DMT2) está aumentando de forma exponencial en todo el mundo, habiéndose comprobado que estos pacientes tienen mayor riesgo de presentar fracturas óseas, con respecto a la población sana, por lo que resulta de gran relevancia el conocimiento del efecto de los fármacos antidiabéticos sobre el metabolismo óseo.

Métodos
Estudio estadístico descriptivo, retrospectivo, de 106 pacientes en tratamiento con seis grupos de fármacos antidiabéticos: insulina, inhibidores de dipeptidilpeptidasa 4 (iDPP4), agonistas del receptor del péptido similar al glucagón tipo 1 (arGLP1), sulfonilureas, inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) y pioglitazona, en los que se determinaron osteocalcina (OC), fosfatasa alcalina ósea (FAO) y telopéptido C-terminal del colágeno tipo 1 o beta-crosslaps (β-CTx).

Resultados
Se encontraron concentraciones más elevadas de β-CTx en los pacientes tratados con pioglitazona que en los tratados con iDPP4 (p=0,035), iSGLT2 (p=0,020) y con arGLP1 (p<0,001), siendo los pacientes tratados con arGLP1 los que presentaron las concentraciones más bajas de β-CTx.

Conclusiones
El tipo de tratamiento antidiabético recibido en pacientes que padecen DMT2 puede afectar el remodelado óseo. En nuestro estudio los pacientes que fueron tratados con pioglitazona mostraron las concentraciones más elevadas de β-CTx con respecto al resto de grupos de fármacos, lo cual parece indicar la conveniencia de evitar estos fármacos, sobre todo en mujeres postmenopáusicas con DMT2. Los fármacos arGLP1 presentaron los valores más bajos de β-CTx, por lo que podrían ejercer un efecto beneficioso sobre el metabolismo óseo.