bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bereavement in childhood and young adulthood and the risk of atrial fibrillation: a population-based cohort study from Denmark and Sweden
Authors: Chen Hua , Janszky Imre , Rostila Mikael , Wei Dang , Yang Fen , Li Jiong , László Krisztina D. 
Published: January 2023

Abstract
Background
Adverse childhood life events are associated with increased risks of hypertension, ischemic heart disease, and stroke later in life. Limited evidence also suggests that stress in adulthood may increase the risk of atrial fibrillation (AF). Whether childhood adversity may lead to the development of AF is unknown. We investigated whether the loss of a parent or sibling in childhood is associated with an increased risk of AF and compared this effect to that of similar losses in young adulthood.

Methods
We studied 6,394,975 live-born individuals included in the Danish (1973–2018) and Swedish Medical Birth Registers (1973–2014). We linked data from several national registers to obtain information on the death of parents and siblings and on personal and familial sociodemographic and health-related factors. We analyzed the association between bereavement and AF using Poisson regression.

Results
Loss of a parent or sibling was associated with an increased AF risk both when the loss occurred in childhood and in adulthood; the adjusted incident rate ratios and 95% confidence intervals were 1.24 (1.14–1.35) and 1.24 (1.16–1.33), respectively. Bereavement in childhood was associated with AF only if losses were due to cardiovascular diseases or other natural causes, while loss in adulthood was associated with AF not only in case of natural deaths, but also unnatural deaths. The associations did not differ substantially according to age at loss and whether the deceased was a parent or a sibling.

Conclusions
Bereavement both in childhood and in adulthood was associated with an increased AF risk.
Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies—pharmacovigilance database analysis with real-world data validation
Authors: Guo Xue-Jun , Cai Xiao-Ting , Rong Zi-Xuan , Zhang Yan-Pei , Wen Yu-Xiang , Bai Xue , Wang Jian , Fu Qiang John , Guo Ze-Qin , Long Li-Li , Ma Si-Cong , Tang Xin-Ran , Liu Li , Guan Jian , Dong Zhong-Yi , Wu De-Hua 
Published: January 2023

Abstract
Background
Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized.

Methods
A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation.

Results
Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05–8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60–184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78–1.04; P = 0.160) and 1.49 (95% CI, 0.95–2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34–50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89–7.92; P = 0.12) and 0.66 (95% CI, 0.03–4.55; P = 0.71), respectively, using ICI monotherapy as reference.

Conclusions
Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.
Early contribution of germline and nevi genetic alterations to a rapidly-progressing cutaneous melanoma patient: a case report
Authors: Mordoh Ana , Triviño Pardo Juan Carlos , Carri Ibel , Barrio María Marcela , Mordoh José , Aris Mariana 
Published: January 2023

AbstractBackgroundCutaneous melanoma is the skin cancer with the highest mutational burden and metastatic rate. Early genetic alterations and biomarkers of distant progression are a point of interest. In addition to germline-susceptibility loci, almost 30% of melanomas arise from precursor benign nevi lesions, providing a source for malignant transformation.Case presentationPatient#009 developed a cutaneous melanoma over a nevus, followed by progression to regional and distant metastases in months, unresponsive to targeted therapy. To search for the genetic contribution to this rapid progression, a longitudinal analysis was performed through WES of germline, nevi, primary tumor, and a metastatic lymph node. Differential SNP/INDEL and CNV gene alterations, with functional impact on key pathways and cancer hallmarks in each step of evolution, were discerned. Tumor-associated nevus was, for the first time, split into two sections, distant and adjacent to the primary tumor, to study its heterogeneity.Shared SNP alterations, with stable allele fraction from germline to metastasis were detected, mainly affecting DNA repair genes and promoting genome instability. Early somatic alterations, shared by nevi and primary and metastatic tumors, included BRAFV600Eand focal copy-loss of several genes, acquiring additional cancer hallmarks. Phylogenetic analyses revealed that these common somatic alterations would provide a “bridge”, allowing progression from a benign to a malignant state. Distant and adjacent nevi were rich in alterations, presenting differential SNP and CNV alterations. Upon tumor transformation, a marked increase in CNV over SNP alterations was determined. Both the number of SNP and CNV-affected genes, including known driver genes, increased throughout progression, although TMB levels remained lower than expected for melanoma. Typical alterations in BRAFV600Etumors related to intrinsic resistance to targeted therapy were found, including BRAF amplification and loss of PTEN, CDKN2A/B, and TP53 surveillance genes. Finally, numerous metastatic alterations were detected, further promoting tumor progression.ConclusionsIn this patient, longitudinal WES analysis revealed a sequential and cumulative pattern of genetic alterations, where germline and nevi somatic events contributed early to its rapid clinical progression. In this case report, we found tumor-associated nevi as genetically heterogeneous precursor entities, in which potential prognostic biomarkers should be studied prospectively.
In ‘real world’ patients with COPD, exacerbation history, and not blood eosinophils, is the most reliable predictor of future exacerbations
Authors: Worth Heinrich , Buhl Roland , Criée Carl-Peter , Kardos Peter , Gückel Eva , Vogelmeier Claus F. 
Published: January 2023

Abstract
Introduction
There is an interest in the role of blood eosinophils for predicting inhaled corticosteroid (ICS) response in chronic obstructive pulmonary disease (COPD). Most data are from interventional clinical studies; data from unselected real-world populations may help better inform treatment decisions. DACCORD is a non-interventional real-world study. Cohort 3 recruited patients with COPD who had received triple therapy for ≥ 6 months; prior to entry patients either continued triple therapy, or switched to a long-acting muscarinic antagonist/long-acting beta2-agonist (LABA/LAMA), and were followed for 12 months.

Methods
For these post-hoc analyses, patients were divided into four groups based on exacerbation history and baseline blood eosinophil count (< 100 vs. > 300 cells/µL). Exacerbation rates were calculated overall and for the two treatments.

Results
Among the 430 patients in the current analyses, the largest groups had low exacerbation history with high (44.2%) or low eosinophils (36.7%). Most patients did not exacerbate during follow-up (68.8% overall; 83.2% and 63.7% with LABA/LAMA and triple therapy). The highest exacerbation rates were in groups with high exacerbation history, differing significantly in the overall analyses from those with low exacerbation history (matched by eosinophil count); rates did not differ when grouped by eosinophil count (matched by exacerbation history).

Conclusions
Although most patients in these analyses did not exacerbate during follow-up, whereas exacerbation history is a predictor of future exacerbations, blood eosinophil count is not. This suggests that although eosinophil count may help to guide ICS initiation, this is less of a consideration when ‘stepping-down’ from triple therapy to a LABA/LAMA
Combination therapy with oncolytic viruses and immune checkpoint inhibitors in head and neck squamous cell carcinomas: an approach of complementary advantages
Authors: Dong Hui , Li Mengli , Yang Chen , Wei Wei , He Xianglei , Cheng Gang , Wang Shibing 
Published: January 2023

AbstractSquamous cell carcinomas are the most common head and neck malignancies. Significant progress has been made in standard therapeutic methods combining surgery, radiation, and chemotherapy. Nevertheless, the 5-year survival rate remains at 40–50%. Immune checkpoint inhibitors (ICIs) are a new strategy for treating head and neck squamous cell carcinomas (HNSCCs). Still, the overall response and effective rates are poor, as HNSCCs are ‘cold’ tumors with an immunosuppressive tumor microenvironment (TME), limiting ICI’s beneficial effects. In this case, transforming the tumor suppression microenvironment before using ICIs could be helpful. Oncolytic viruses (OVs) can transform cold tumors into hot tumors, improving the situation. Talimogene laherparepvec (T-VEC), oncolytic immunotherapy authorized for advanced melanoma, also showed good safety and antitumor activity in treating head and neck cancer and pancreatic cancer. In combination with pembrolizumab, T-Vec may have more anticancer efficacy than either drug alone. Therefore, understanding the mechanisms underpinning OVs and their potential synergism with ICIs could benefit patients with HNSCC.
Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults
Authors: Joof Fatou , Hartmann Elena , Jarvis Alison , Colley Alhassan , Cross James H. , Avril Marion , Prentice Andrew M. , Cerami Carla 
Published: January 2023

AbstractBackgroundPolymorphisms inATP2B4coding for PMCA4b, the primary regulator of erythrocyte calcium concentration, have been shown by GWAS and cross-sectional studies to protect against severe malaria but the mechanism remains unknown.MethodsUsing a recall-by-genotype design, we investigated the impact of a common haplotype variant inATP2B4using in vitro assays that model erythrocyte stage malaria pathogenesis. Ninety-six donors representing homozygotes (carriers of the minor alleles, T/T (variant), heterozygote T/C and wildtype C/C (ancestral)) carriers of the tagging SNP rs1541252 were selected from a cohort of over 12,000 participants in the Keneba Biobank.ResultsRed blood cells (RBCs) from homozygotes showed reduced PMCA4b protein expression (mean fluorescence intensities (MFI = 2428 ± 124, 3544 ± 159 and 4261 ± 283], for homozygotes, heterozygotes and wildtypes respectively, p < 0.0001) and slower rates of calcium expulsion (calcium t½ ± SD = 4.7 ± 0.5, 1.8 ± 0.3 and 1.9 ± 0.4 min, p < 0.0001). Growth of aPlasmodium falciparumlaboratory strain (FCR3) and two Gambian field isolates was decreased in RBCs from homozygotes compared to heterozygotes and wildtypes (p < 0.01). Genotype group did not affect parasite adhesion in vitro orvar-gene expression in malaria-infected RBCs. Parasite growth was inhibited by a known inhibitor of PMCA4b, aurintricarboxylic acid (IC50 = 122uM CI: 110–134) confirming its sensitivity to calcium channel blockade.ConclusionThe data support the hypothesis that thisATP2B4genotype, common in The Gambia and other malaria-endemic areas, protects against severe malaria through the suppression of parasitaemia during an infection. Reduction in parasite density plays a pivotal role in disease outcome by minimizing all aspects of malaria pathogenesis. Follow up studies are needed to further elucidate the mechanism of protection and to determine if thisATP2B4genotype carries a fitness cost or increases susceptibility to other human disease.
Why are they “unreached”? Macro and Meso determinants of health care access in hard to reach areas of Odisha, India
Authors: Nallala Srinivas , Ghosh Upasona , Desaraju Shyama Sundari , Kadam Shridhar , Kadarpeta Rahul Reddy , Van Belle Sara 
Published: January 2023

AbstractBackgroundReaching hard to reach populations is key to reduce health inequities. Despite targeted interventions, status of crucial public health indicators like neonatal and maternal mortality is still far from optimal. Complex interplay of social determinants can influence both communities and health care workers to effectively access each other. We argue that culturally sensitive and contextually relevant healthcare provision has potential to increase health care utilization by the vulnerable communities living in remote areas.MethodsThe study is an exploratory case study using rapid ethnographic techniques to understand the interplay of social determinants in hard to reach areas of Odisha state, India. We used in-depth interviews, focus group discussion, participatory action research and key informant interviews as tools for data collection. The analysis of data has been guided by thematic analysis approach.ResultsWe found that there are further layers within the designated hard to reach areas and those can be designated as-i) extremely remote ii) remote and iii) reachable areas. Degree of geographic difficulties and cultural dynamics are deciding the ‘perceived’ isolation and interaction with health care providers in hard to reach areas. This ultimately leads to impacting the utilization of the facilities. At extremely remote areas, felt health needs are mainly fulfilled by traditional healers and ethno-medical practices. In reachable areas, people are more prone to seek care from the public health facilities because of easy accessibility and outreach. Being in middle people in remote areas, diversify health care seeking depending upon social (e.g. patient’s gender) economic (e.g. avoid catastrophic expenditure) and health system (timely availability of health human resources, language barriers) factors.ConclusionOur research highlights the need to value and appreciate different worldviews, beliefs and practices, and their understanding of and engagement with the pluralistic health care system around them. Other than pursuing the ‘mainstreaming’ of a standardized health system model across hard to reach areas, strategies need to be adaptive as per local factors. To handle that existing policies need revision with a focus on culturally sensitive and contextual care provision.
NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a “One-Stone-Two-Birds” manner
Authors: Wu Guanghao , Su Qihang , Li Jie , Xue Chao , Zhu Jie , Cai Qiuchen , Huang Jingbiao , Ji Shaoyang , Cheng Biao , Ge Hengan 
Published: January 2023

Abstract
Background
Tendinopathy is the leading sports-related injury and will cause severe weakness and tenderness. Effective therapy for tendinopathy remains limited, and extracellular vesicles (EVs) derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) have demonstrated great potential in tendinopathy treatment; however, the influence of aging status on EV treatment has not been previously described.

Results
In this study, it was found that ADMSCs derived from old mice (ADMSCold) demonstrated remarkable cellular senescence and impaired NAD+ metabolism compared with ADMSCs derived from young mice (ADMSCyoung). Lower NAMPT contents were detected in both ADMSCold and its secreted EVs (ADMSCold-EVs). Advanced animal experiments demonstrated that ADMSCyoung-EVs, but not ADMSCold-EVs, alleviated the pathological structural, functional and biomechanical properties in tendinopathy mice. Mechanistic analyses demonstrated that ADMSCyoung-EVs improved cell viability and relieved cellular senescence of tenocytes through the NAMPT/SIRT1/PPARγ/PGC-1α pathway. ADMSCyoung-EVs, but not ADMSCold-EVs, promoted phagocytosis and M2 polarization in macrophages through the NAMPT/SIRT1/Nf-κb p65/NLRP3 pathway. The macrophage/tenocyte crosstalk in tendinopathy was influenced by ADMSCyoung-EV treatment and thus it demonstrated "One-Stone-Two-Birds" effects in tendinopathy treatment.

Conclusions
This study demonstrates an effective novel therapy for tendinopathy and uncovers the influence of donor age on curative effects by clarifying the detailed biological mechanism.

Graphical Abstract
Breastfeeding, socioeconomic status, and long-term postpartum weight retention
Authors: Foster Saralyn F. , Vazquez Christian , Cubbin Catherine , Nichols Amy R. , Rickman Rachel R. , Widen Elizabeth M. 
Published: January 2023

Abstract
Background
Almost half of all pregnant women in the United States gain weight above Institute of Medicine gestational weight gain guidelines. Breastfeeding has been shown to reduce weight retention in the first year postpartum; however, women with lower socioeconomic status (SES) tend to initiate breastfeeding less often than women with higher SES. We investigated associations between duration of breastfeeding with mother’s long-term postpartum weight status at 4–10 years and evaluated whether the associations varied by SES.

Methods
Maternal and infant dyads (N = 2144 dyads) are from the Geographic Research on Wellbeing survey (GROW), 2012–2013, a long-term, cross-sectional follow-up of the Maternal and Infant Health Assessment (MIHA) based in California, USA. Pre-pregnancy body mass index (BMI) was obtained from self-report of height and weight during MIHA, while breastfeeding history and self-report of current body weight was collected at the 4–10 year GROW postpartum visit. SES score was derived from a composite score of percent federal poverty level and education and was dichotomized into High and Low SES groups at a score of three. Multivariable linear regression was used to examine association between breastfeeding and maternal weight status, and to examine for effect modification by SES.

Results
Average long-term weight retention 4–10 years postpartum was 4.0 kg. Fewer lower SES vs. higher SES women breast fed at least six months (51% versus 70%, p < .001) or ever breastfed (74% versus 89%, P < .001). Women who breastfed at least six months had lower long-term postpartum weight retention compared to those who did not (b = -1.06 kg, (-1.93, 0.25); p = 0.01); however, these association did not vary by SES.

Conclusion
Six months of breastfeeding is associated with lower BMI at 4–10 years and lower body weight, and effects do not vary by SES. Future policies and guidelines should consider building an infrastructure that is supportive of longer breastfeeding duration. Moreover, further research is needed to identify the impact of additional behavioral and environmental factors on long-term maternal weight status. Understanding the drivers of excessive weight retention pospartum can help us not only improve the pregnant person’s health but the health of their children.
Dosimetric comparison of deformable image registration and synthetic CT generation based on CBCT images for organs at risk in cervical cancer radiotherapy
Authors: Chang Yankui , Liang Yongguang , Yang Bo , Qiu Jie , Pei Xi , Xu Xie George 
Published: January 2023

Abstract
Objective
Anatomical variations existing in cervical cancer radiotherapy treatment can be monitored by cone-beam computed tomography (CBCT) images. Deformable image registration (DIR) from planning CT (pCT) to CBCT images and synthetic CT (sCT) image generation based on CBCT are two methods for improving the quality of CBCT images. This study aims to compare the accuracy of these two approaches geometrically and dosimetrically in cervical cancer radiotherapy.

Methods
In this study, 40 paired pCT-CBCT images were collected to evaluate the accuracy of DIR and sCT generation. The DIR method was based on a 3D multistage registration network that was trained with 150 paired pCT-CBCT images, and the sCT generation method was performed based on a 2D cycle-consistent adversarial network (CycleGAN) with 6000 paired pCT-CBCT slices for training. Then, the doses were recalculated with the CBCT, pCT, deformed pCT (dpCT) and sCT images by a GPU-based Monte Carlo dose code, ArcherQA, to obtain DoseCBCT, DosepCT, DosedpCT and DosesCT. Organs at risk (OARs) included small intestine, rectum, bladder, spinal cord, femoral heads and bone marrow, CBCT and pCT contours were delineated manually, dpCT contours were propagated through deformation vector fields, sCT contours were auto-segmented and corrected manually.

Results
The global gamma pass rate of DosesCT and DosedpCT was 99.66% ± 0.34%, while that of DoseCBCT and DosedpCT was 85.92% ± 7.56% at the 1%/1 mm criterion and a low-dose threshold of 10%. Based on DosedpCT as uniform dose distribution, there were comparable errors in femoral heads and bone marrow for the dpCT and sCT contours compared with CBCT contours, while sCT contours had lower errors in small intestine, rectum, bladder and spinal cord, especially for those with large volume difference of pCT and CBCT.

Conclusions
For cervical cancer radiotherapy, the DIR method and sCT generation could produce similar precise dose distributions, but sCT contours had higher accuracy when the difference in planning CT and CBCT was large.
Clinical effects of early debridement, internal fixation, and Masquelet technique for childhood chronic haematogenous osteomyelitis of long bones
Authors: Shi Jian , Yang Xiaoyong , Song Muguo , Zhang Xijiao , Xu Yongqing 
Published: January 2023

Abstract
Background
Childhood chronic haematogenous osteomyelitis (CCHOM) is a severe condition in paediatric patients. The optimal timing of debridement and the subsequent method of bone reconstruction in CCHOM patients remain controversial. The purpose of this study was to assess the treatment efficacy of Masquelet technique with early debridement and internal fixation in CCHOM of long bones.

Methods
Between January 2016 and January 2021, a total of 21 patients (18 males, 3 females) with CCHOM of long bone were included. The mean age was 10.4 years (range, 2–18 years). All cases were treated by a two-stage surgical protocol of Masquelet technique. In the first stage, aggressive debridement, sequestrectomy, and inducing membrane by bone cement spacer were performed after definite diagnosis. In the second stage, cement spacer was removed, and autologous and allogeneic bone was grafted. Internal fixation was used for the first and/or second stage depending on stability requirements. The patients’ clinical and imaging results were retrospectively analysed.

Results
The mean follow-up was 31.7 months (range, 21–61 months). None of the patients experienced recurrence of infection. Radiographic bone union time was 4.3 months (range, 2.5–11 months). Five cases underwent re-operation due to complications such as bone resorption or refracture. By the last follow-up visit, bones had healed and all of the patients had resumed daily living and sports activities.

Conclusion
The Masquelet technique with early debridement and internal fixation is a viable surgical method for the management of large long bone defects of CCHOM patients.