bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes
Authors: Soomro Misbah Younus , Khan Saqib Raza , Muhammad Hafiz , Ahmad Sujjawal , Zehra Nawazish , Ali Insia , Samar Mirza Rameez , Hameed Arif , Moosajee Munira , Rashid Yasmin Abdul 
Published: April 2024

Abstract
Background
Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape.

Methods
In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates—no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests.

Results
We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0–1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups.

Conclusion
Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.
Continuing the conversation: a cross-sectional study about the effects of work-related adverse events on the mental health of Dutch (resident) obstetrician-gynaecologists (ObGyns)
Authors: Baas Melanie A.M. , Stramrood Claire A.I. , Molenaar Jolijn E. , van Baar Petra M. , Vanhommerig Joost W. , van Pampus Maria G. 
Published: April 2024

Abstract
Background
Obstetrician-Gynaecologists (ObGyns) frequently face work-related adverse events such as severe obstetric complications and maternal or neonatal deaths. In 2014, the WATER-1 study showed that ObGyns are at risk of developing work-related posttraumatic stress disorder (PTSD), while many hospitals lacked a professional support system. The aim of the present study is to evaluate the current prevalence of work-related traumatic events and mental health problems among Dutch ObGyns, as well as to examine the current and desired support.

Methods
In 2022, an online questionnaire was sent to all members of the Dutch Society of Obstetrics and Gynaecology (NVOG), including resident and attending ObGyns. The survey included questions about experienced work-related events, current and desired coping strategies, and three validated screening questionnaires for anxiety, depression, and PTSD (HADS, TSQ, and PCL-5).

Results
The response rate was 18.8% and 343 questionnaires were included in the analysis. Of the respondents, 93.9% had experienced at least one work-related adverse event, 20.1% had faced a complaint from the national disciplinary board, and 49.4% had considered leaving the profession at any moment in their career. The prevalence rates of clinically relevant anxiety, depression, and psychological distress were 14.3, 4.4, and 15.7%, respectively. The prevalence of work-related PTSD was 0.9% according to DSM-IV and 1.2% according to DSM-5. More than half of the respondents (61.3%) reported the presence of a structured support protocol or approach in their department or hospital, and almost all respondents (92.6%) rated it as sufficient.

Conclusions
The percentages of anxiety, depression, psychological distress and PTSD are comparable to the similar study performed in 2014. Most Dutch ObGyns experience adverse events at work, which can be perceived as traumatic and, in certain cases, may lead to the development of PTSD. Structured support after adverse work-related events is now available in almost two-thirds of workplaces, and was mostly experienced as good. Despite substantial improvements in the availability and satisfaction of professional support after work-related adverse events, the prevalence rates of mental problems remain considerable, and it is imperative to sustain conversation about the mental well-being of ObGyns.
Identification and bioinformatics analysis of lncRNAs in serum of patients with ankylosing spondylitis
Authors: Kou Jianqiang , Bie Yongchen , Liu Mingquan , Wang Liqin , Liu Xiangyun , Sun Yuanliang , Zheng Xiujun 
Published: April 2024

Abstract
Objectives
The aim of this study was to explore the long non-coding RNA (lncRNA) expression profiles in serum of patients with ankylosing spondylitis (AS). The role of these lncRNAs in this complex autoimmune situation needs to be evaluated.

Methods
We used high-throughput whole-transcriptome sequencing to generate sequencing data from three patients with AS and three normal controls (NC). Then, we performed bioinformatics analyses to identify the functional and biological processes associated with differentially expressed lncRNAs (DElncRNAs). We confirmed the validity of our RNA-seq data by assessing the expression of eight lncRNAs via quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 AS and 20 NC samples. We measured the correlation between the expression levels of lncRNAs and patient clinical index values using the Spearman correlation test.

Results
We identified 72 significantly upregulated and 73 significantly downregulated lncRNAs in AS patients compared to NC. qRT-PCR was performed to validate the expression of selected DElncRNAs; the results demonstrated that the expression levels of MALAT1:24, NBR2:9, lnc-DLK1-35:13, lnc-LARP1-1:1, lnc-AIPL1-1:7, and lnc-SLC12A7-1:16 were consistent with the sequencing analysis results. Enrichment analysis showed that DElncRNAs mainly participated in the immune and inflammatory responses pathways, such as regulation of protein ubiquitination, major histocompatibility complex class I-mediated antigen processing and presentation, MAPkinase activation, and interleukin-17 signaling pathways. In addition, a competing endogenous RNA network was constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs (MALAT1:24 and NBR2:9). We further found the expression of MALAT1:24 and NBR2:9 to be positively correlated with disease severity.

Conclusion
Taken together, our study presents a comprehensive overview of lncRNAs in the serum of AS patients, thereby contributing novel perspectives on the underlying pathogenic mechanisms of this condition. In addition, our study predicted MALAT1 has the potential to be deeply involved in the pathogenesis of AS.
A qualitative study of the experiences of interdisciplinary nurses during the COVID-19 outbreak following the announcement of the “Ten new guidelines” in China
Authors: Huang Li-Li , Wang Wei-Fen , Hong Wei-Wen , Huang Xian-Dan , Guan Xian-Hua 
Published: April 2024

Abstract
Background
On December 7, 2022, the Joint Prevention and Control Mechanism of China’s State Council released the “Ten New Guidelines” to optimize the coronavirus disease 2019 (COVID-19) prevention policies further. This signaled a broader shift from “dynamic clearing” to “coexisting with the virus” nationwide.

Objective
This study aims to examine the experiences and perspectives of interdisciplinary nurses during the COVID-19 outbreak in China after the implementation of the “Ten New Guidelines”. The goal is to understand the challenges faced by this unique nursing group and inform organizational support to bolster their well-being and resilience.

Methods
Two tertiary hospitals in southeastern Zhejiang Province were selected, with interdisciplinary nurses chosen as subjects. A constructivist qualitative research approach was employed, using semi-structured face-to-face interviews. Research data were collected through interviews and analyzed using content analysis.

Results
Fifteen interdisciplinary nurses were included in this study. The analysis revealed four main themes and nine sub-themes. The main themes were: (1) ineffective organizational support (inadequate organizational care, poor PPE, excessive workload), (2) physiological distress after contracting COVID-19 (extreme physical fatigue, leakage of urine due to severe coughing), (3) fear of being wrong (fear of being reprimanded in public, psychological anxiety), and (4) family responsibility anxiety (difficulty of loyalty and filial piety, obligations to their children).

Conclusion
We provide new evidence that organizations must proactively address the support, training, and communication needs of staff, particularly interdisciplinary nurses, to supplement epidemic containment. This is also essential in helping mitigate the work-family conflicts such roles can create.
Multilocus pathogenic variants contribute to intrafamilial clinical heterogeneity: a retrospective study of sibling pairs with neurodevelopmental disorders
Authors: Bozkurt-Yozgatli Tugce , Pehlivan Davut , Gibbs Richard A. , Sezerman Ugur , Posey Jennifer E. , Lupski James R. , Coban-Akdemir Zeynep 
Published: April 2024

Abstract
Background
Multilocus pathogenic variants (MPVs) are genetic changes that affect multiple gene loci or regions of the genome, collectively leading to multiple molecular diagnoses. MPVs may also contribute to intrafamilial phenotypic variability between affected individuals within a nuclear family. In this study, we aim to gain further insights into the influence of MPVs on a disease manifestation in individual research subjects and explore the complexities of the human genome within a familial context.

Methods
We conducted a systematic reanalysis of exome sequencing data and runs of homozygosity (ROH) regions of 47 sibling pairs previously diagnosed with various neurodevelopmental disorders (NDD).

Results
We found siblings with MPVs driven by long ROH regions in 8.5% of families (4/47). The patients with MPVs exhibited significantly higher FROH values (p-value = 1.4e-2) and larger total ROH length (p-value = 1.8e-2). Long ROH regions mainly contribute to this pattern; the siblings with MPVs have a larger total size of long ROH regions than their siblings in all families (p-value = 6.9e-3). Whereas the short ROH regions in the siblings with MPVs are lower in total size compared to their sibling pairs with single locus pathogenic variants (p-value = 0.029), and there are no statistically significant differences in medium ROH regions between sibling pairs (p-value = 0.52).

Conclusion
This study sheds light on the significance of considering MPVs in families with affected sibling pairs and the role of ROH as an adjuvant tool in explaining clinical variability within families. Identifying individuals carrying MPVs may have implications for disease management, identification of possible disease risks to different family members, genetic counseling and exploring personalized treatment approaches.
Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis
Authors: Kraaijvanger Raisa , Janssen Bonás Montse , Grutters Jan C. , Paspali Ioanna , Veltkamp Marcel , de Kleijn Dominique P. V. , van Moorsel Coline H. M. 
Published: April 2024

Abstract
Background
Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking.

Objective
In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy.

Methods
Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment).

Results
Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032).

Conclusion
This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.
Factors associated with malaria vaccine uptake in Nsanje district, Malawi
Authors: Simbeye Atusaye J. , Kumwenda Save , Cohee Lauren M. , Omondi Dickens , Masibo Peninah K. , Wao Hesborn , Awandu Shehu S. 
Published: April 2024

Abstract
Background
Malaria remains a significant global health burden affecting millions of people, children under 5 years and pregnant women being most vulnerable. In 2019, the World Health Organization (WHO) endorsed the introduction of RTS,S/AS01 malaria vaccine as Phase IV implementation evaluation in three countries: Malawi, Kenya and Ghana. Acceptability and factors influencing vaccination coverage in implementing areas is relatively unknown. In Malawi, only 60% of children were fully immunized with malaria vaccine in Nsanje district in 2021, which is below 80% WHO target. This study aimed at exploring factors influencing uptake of malaria vaccine and identify approaches to increase vaccination.

Methods
In a cross-sectional study conducted in April–May, 2023, 410 mothers/caregivers with children aged 24–36 months were selected by stratified random sampling and interviewed using a structured questionnaire. Vaccination data was collected from health passports, for those without health passports, data was collected using recall history. Regression analyses were used to test association between independent variables and full uptake of malaria vaccine.

Results
Uptake of malaria vaccine was 90.5% for dose 1, but reduced to 87.6%, 69.5% and 41.2% for dose 2, 3, and 4 respectively. Children of caregivers with secondary or upper education and those who attended antenatal clinic four times or more had increased odds of full uptake of malaria vaccine [OR: 2.43, 95%CI 1.08–6.51 and OR: 1.89, 95%CI 1.18–3.02], respectively. Children who ever suffered side-effects following immunization and those who travelled long distances to reach the vaccination centre had reduced odds of full uptake of malaria vaccine [OR: 0.35, 95%CI 0.06–0.25 and OR: 0.30, 95%CI 0.03–0.39] respectively. Only 17% (n = 65) of mothers/caregivers knew the correct schedule for vaccination and 38.5% (n = 158) knew the correct number of doses a child was to receive.

Conclusion
Only RTS,S dose 1 and 2 uptake met WHO coverage targets. Mothers/caregivers had low level of information regarding malaria vaccine, especially on numbers of doses to be received and dosing schedule. The primary modifiable factor influencing vaccine uptake was mother/caregiver knowledge about the vaccine. Thus, to increase the uptake Nsanje District Health Directorate should strengthen communities’ education about malaria vaccine. Programmes to strengthen mother/caregiver knowledge should be included in scale-up of the vaccine in Malawi and across sub-Saharan Africa.
Elective neck dissection versus elective neck irradiation in cT3/4N0 maxillary sinus squamous cell carcinoma: a propensity score matching analysis
Authors: Chen Min , Gu Hefeng , Xuan Guihong , Ma Lan , Tu Sunyu , Li Min 
Published: April 2024

Abstract
Background
Maxillary sinus squamous cell carcinoma (MS-SCC) is an infrequent malignancy, and determining the optimal neck management for patients with cT3/4N0 MS-SCC remains a topic of ongoing debate. The purpose of this study was to compare the prognoses and quality of life outcomes of patients who underwent either elective neck dissection (END) or elective neck irradiation (ENI) for cT3/4N0 MS-SCC.

Methods
In this retrospective study, we enrolled patients with surgically treated cT3/4N0 MS-SCC, and the impact of different neck management strategies on regional control and disease-specific survival was compared using propensity score matching. The effect of surgical intervention on quality of life was evaluated using the Mann-Whitney U test.

Results
Of the 120 patients included, 36 underwent END. After propensity score matching, our analysis indicated that END did not lead to superior outcomes than ENI, as demonstrated by comparable rates of regional control (p = 0.990) and disease-specific survival (p = 0.999). However, in the 70 returned questionnaires, patients who underwent END reported higher scores in the domains of appearance, chewing, and speech than did patients who underwent ENI.

Conclusions
Our findings suggest that while END and ENI contribute to similar prognoses, END yields superior functional outcomes.
GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy
Authors: Fu Qun , Zhang Yi-Bao , Shi Chang-Xi , Jiang Ming , Lu Kai , Fu Zi-Hui , Ruan Jia-Ping , Wu Jing , Gu Xiao-Ping 
Published: April 2024

Abstract
Background
Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE.

Methods
C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus.

Results
CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities.

Conclusions
Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.
Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis
Authors: Şenkesen Öznur , Tezcanlı Evrim , Alkaya Fadime , İspir Burçin , Çatlı Serap , Yeşil Abdullah , Bezirganoglu Ebrar , Turan Sezgi , Köksal Canan , Güray Gülay , Hacıislamoğlu Emel , Durmuş İsmail Faruk , Çavdar Şeyma , Aksu Telat , Çolak Nurten , Küçükmorkoç Esra , Doğan Mustafa , Ercan Tülay , Karaköse Fatih , Alpan Vildan , Ceylan Cemile , Poyraz Gökhan , Nalbant Nilgül , Kınay Şeyda , İpek Servet , Kayalılar Namık , Tatlı Hamza , Zhu Mingyao 
Published: April 2024

Abstract
Objective
This study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution.

Methods
Anonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy.

Results
All techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes.

Conclusion
Modern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection.