bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-proxy analyses of a mid-15th century Middle Iron Age Bantu-speaker palaeo-faecal specimen elucidates the configuration of the ‘ancestral’ sub-Saharan African intestinal microbiome
Authors: Rifkin Riaan F. , Vikram Surendra , Ramond Jean-Baptiste , Rey-Iglesia Alba , Brand Tina B. , Porraz Guillaume , Val Aurore , Hall Grant , Woodborne Stephan , Le Bailly Matthieu , Potgieter Marnie , Underdown Simon J. , Koopman Jessica E. , Cowan Don A. , Van de Peer Yves , Willerslev Eske , Hansen Anders J. 
Published: May 2020

AbstractBackgroundThe archaeological incidence of ancient human faecal material provides a rare opportunity to explore the taxonomic composition and metabolic capacity of the ancestral human intestinal microbiome (IM). Here, we report the results of the shotgun metagenomic analyses of an ancient South African palaeo-faecal specimen.MethodsFollowing the recovery of a single desiccated palaeo-faecal specimen from Bushman Rock Shelter in Limpopo Province, South Africa, we applied a multi-proxy analytical protocol to the sample. The extraction of ancient DNA from the specimen and its subsequent shotgun metagenomic sequencing facilitated the taxonomic and metabolic characterisation of this ancient human IM.ResultsOur results indicate that the distal IM of the Neolithic ‘Middle Iron Age’ (c. AD 1460) Bantu-speaking individual exhibits features indicative of a largely mixed forager-agro-pastoralist diet. Subsequent comparison with the IMs of the Tyrolean Iceman (Ötzi) and contemporary Hadza hunter-gatherers, Malawian agro-pastoralists and Italians reveals that this IM precedes recent adaptation to ‘Western’ diets, including the consumption of coffee, tea, chocolate, citrus and soy, and the use of antibiotics, analgesics and also exposure to various toxic environmental pollutants.ConclusionsOur analyses reveal some of the causes and means by which current human IMs are likely to have responded to recent dietary changes, prescription medications and environmental pollutants, providing rare insight into human IM evolution following the advent of the Neolithicc. 12,000 years ago.
Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?
Authors: Xu Tianmin , Gao Haoyue 
Published: May 2020

Abstract5-Methylcytosine (5mC) is considered as a common epigenetic modification that plays an important role in the regulation of gene expression. At the same time, 5-hydroxymethylcytosine (5hmC) has been found as an emerging modification of cytosine bases of recent years. Unlike 5mC, global 5hmC levels vary from tissues that have differential distribution both in mammalian tissues and in the genome. DNA hydroxymethylation is the process that 5mC oxidates into 5hmC with the catalysis of TET (ten-eleven translocation) enzymes. It is an essential option of DNA demethylation, which modulates gene expression by adjusting the DNA methylation level. Various factors can regulate the demethylation of DNA, such as environmental toxins and mental stress. In this review, we summarize the progress in the formation of 5hmC, and obtaining 5hmC in a cell-free DNA sample presents multiple advantages and challenges for the subject. Furthermore, the clinical potential for 5hmC modification in dealing with cancer early diagnosis, prognostic evaluation, and prediction of therapeutic effect is also mentioned.
Genetic perspective on the synergistic connection between vesicular transport, lysosomal and mitochondrial pathways associated with Parkinson’s disease pathogenesis
Authors: Smolders Stefanie , Van Broeckhoven Christine 
Published: May 2020

AbstractParkinson’s disease (PD) and atypical parkinsonian syndromes (APS) are symptomatically characterized by parkinsonism, with the latter presenting additionally a distinctive range of atypical features. Although the majority of patients with PD and APS appear to be sporadic, genetic causes of several rare monogenic disease variants were identified. The knowledge acquired from these genetic factors indicated that defects in vesicular transport pathways, endo-lysosomal dysfunction, impaired autophagy-lysosomal protein and organelle degradation pathways, α-synuclein aggregation and mitochondrial dysfunction play key roles in PD pathogenesis. Moreover, membrane dynamics are increasingly recognized as a key player in the disease pathogenesis due lipid homeostasis alterations, associated with lysosomal dysfunction, caused by mutations in several PD and APS genes. The importance of lysosomal dysfunction and lipid homeostasis is strengthened by both genetic discoveries and clinical epidemiology of the association between parkinsonism and lysosomal storage disorders (LSDs), caused by the disruption of lysosomal biogenesis or function. A synergistic coordination between vesicular trafficking, lysosomal and mitochondria defects exist whereby mutations in PD and APS genes encoding proteins primarily involved one PD pathway are frequently associated with defects in other PD pathways as a secondary effect. Moreover, accumulating clinical and genetic observations suggest more complex inheritance patters of familial PD exist, including oligogenic and polygenic inheritance of genes in the same or interconnected PD pathways, further strengthening their synergistic connection.Here, we provide a comprehensive overview of PD and APS genes with functions in vesicular transport, lysosomal and mitochondrial pathways, and highlight functional and genetic evidence of the synergistic connection between these PD associated pathways.
Study on streamflow response to land use change over the upper reaches of Zhanghe Reservoir in the Yangtze River basin
Authors: Chen Yuqi , Niu Jun , Sun Yuqing , Liu Qi , Li Sien , Li Peng , Sun Liqun , Li Qinglan 
Published: May 2020

AbstractThe Zhanghe Reservoir in Yangtze River basin plays a key role in fulfilling the crop water requirements of the irrigation area in its downstream region. This study employs the SWAT (Soil and Water Assessment Tool) model to simulate the variations of Zhanghe Reservoir inflow. The model performed well at monthly timescale, with the values of both NSE and R2 above 0.7. The land use distribution and the structure changes in 1990, 2000, and 2015 are employed to study the reservoir inflow responses to the land use changes in the contributed basin area. In the historical period (1990–2000), the streamflow was decreased by 0.4%, accompanied by the reductions of farmland and grassland area, and the increase of forestry area. The land use scenarios are further designed for considering possible future land use alterations. The low flow responses to the completely forestry cover for the basin is more obvious to the completely grassland cover. Accordingly, the further afforestation may aggravate the drought situation due to the low flow reduction. In addition, the high flow responses are reversed to these two land cover situations. The obtained results are useful for designing future sustainable development strategies for the region.
Thoracoscopic surgery combined with endoscopic creation of a submucosal tunnel for a large complicated esophageal leiomyoma
Authors: Oyama Koki , Ohuchida Kenoki , Shindo Koji , Moriyama Taiki , Hata Yoshitaka , Wada Masafumi , Ihara Eikichi , Nagai Shuntaro , Ohtsuka Takao , Nakamura Masafumi 
Published: May 2020

Abstract
Background
The standard surgical method for symptomatic submucosal tumors (SMTs) or tumors with unclear biological behavior is enucleation. Minimally invasive approaches are usually considered appropriate for surgical enucleation; thus, thoracoscopic and laparoscopic enucleation is performed widely and safely. However, it is sometimes difficult to enucleate large and complicated esophageal tumors using thoracoscopic surgery, and even if rare, there is the risk of requiring thoracotomy or esophagectomy. In the present case, we enucleated a large and complicated leiomyoma safely using a new combined method with endoscopic and thoracoscopic procedures.

Case presentation
A 42-year-old woman presented to our hospital for a detailed examination of an abnormal finding in her health check-up chest X-ray images. She complained of upper abdominal pain after eating, and computed tomography revealed an esophageal tumor measuring 60 mm in length surrounding her lower thoracic esophagus. Esophagogastroduodenoscopy revealed a huge complicated SMT at the esophagogastric junction. Cytological examination with endoscopic ultrasound-guided fine-needle aspiration showed that the tumor was a leiomyoma. To enucleate this large and complicated esophageal SMT safely and without damaging the esophageal mucosa, we performed endoscopic and thoracoscopic procedures. We created a submucosal tunnel, endoscopically, and then performed thoracoscopic surgery to enucleate the tumor completely from the esophageal muscularis. Using these combined procedures, we were able to easily mobilize even a complicated tumor of this size from the mucosa and completed the surgery thoracoscopically without difficulty. As a result, the tumor was dissected safely with a minimal defect in the muscularis and without damaging the mucosa. Finally, we closed the defect in the esophageal muscularis with continuous sutures, thoracoscopically, and closed the entry of the submucosal tunnel using clips, endoscopically.

Conclusions
Using these combined procedures, we safely enucleated a huge complicated esophageal SMT. The increased mobility of the tumor after creating the submucosal tunnel contributed to the minimal defect in the muscular layer and prevented injury to the esophageal mucosa, possibly leading to fewer postoperative complications such as esophageal stenosis and local infection.
Where is the policy? A bibliometric analysis of the state of policy research on medical tourism
Authors: Virani Altaf , Wellstead Adam M. , Howlett Michael 
Published: May 2020

Abstract
Background
It is imperative that researchers studying medical tourism connect their work with policy, so that its real-world challenges can be better understood, and more effectively addressed. This article gauges the scope and evolution of policy thinking in medical tourism research through a bibliometric review of published academic literature, to establish the extent to which researchers apply public policy theories and frameworks in their investigation of medical tourism, or consider the policy imperatives of their work.

Methods
A Boolean search of the Web of Science (WoS) Core Collection was performed to identify policy-related publications on medical tourism. We analyzed the results using bibliometrics and a data visualization software called VOSviewer to identify patterns in knowledge production and underlying network linkages in policy research on the subject.

Results
Our findings suggest that only a small proportion of medical tourism research explicitly addresses policy issues or applies policy paradigms in their study approach. Field-specialized journals serving practitioners publish less research as compared to interdisciplinary social and health policy journals. Moreover, there are significant geographical and disciplinary disparities in the policy-orientation of research, and a predilection towards select policy areas such as reproductive and transplant tourism to the neglect of more holistic governance and health system considerations.

Conclusion
This article is a call to action for greater engagement by policy scholars on medical tourism, and for health researchers to more explicitly consider how their research might contribute to the understanding and resolution of contemporary policy challenges of medical tourism. Failure to clearly and consistently make the policy connection is a lost opportunity for researchers to frame the public debate, and influence policy thinking on medical tourism.
Research on optical 32QAM-OFDM-PON access scheme with different numbers of sub-carriers using DMT modulation
Authors: Shao Yufeng , Long Ying , Wang Anrong , Tan Zefu , Lei Guoping , Hu Zhengquan , Liu Yu , Hu Qinzheng , Wang Zhuang , Yang Jie 
Published: May 2020

AbstractAn optical 32QAM-OFDM-PON system with different numbers of sub-carriers using discrete multitone (DMT) modulation and demodulation is designed and demonstrated by experiment. Electron-optic generation, directly photoelectric detection, and electrical self-mixing reception of 32QAM-OFDM downstream signals are achieved. 5Gb/s 32QAM-OFDM downlink signals with different numbers of sub-carriers are successfully transmitted over 42 km SMF-28. Peak-to average power ratio (PAPR) characteristic, computational complexity and bit error rate (BER) performance are analyzed. The results show that the sub-carriers numbers of 32QAM-OFDM downlink signals should be carefully selected according to the actual requirements, if spectral efficiency, PAPR characteristic, computational complexity and receiver sensitivity are considered.
Protocol for two-arm pragmatic cluster randomized hybrid implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe COPD exacerbation
Authors: Stefan Mihaela S. , Pekow Penelope S. , Shea Christopher M. , Hughes Ashley M. , Hill Nicholas S. , Steingrub Jay S. , Lindenauer Peter K. 
Published: May 2020

AbstractBackgroundCOPD is the fourth leading cause of death in the US, and COPD exacerbations result in approximately 700,000 hospitalizations annually. Patients with acute respiratory failure due to severe COPD exacerbation are treated with invasive (IMV) or noninvasive mechanical ventilation (NIV). Although IMV reverses hypercapnia/hypoxia, it causes significant morbidity and mortality. There is strong evidence that patients treated with NIV have better outcomes, and NIV is recommended as first line therapy in these patients. Yet, several studies have demonstrated substantial variation in the use of NIV across hospitals, leading to preventable morbidity and mortality. Through a series of mixed-methods studies, we have found that successful implementation of NIV requires physicians, respiratory therapists (RTs), and nurses to communicate and collaborate effectively, suggesting that efforts to increase the use of NIV in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, we propose to compare two educational strategies: online education (OLE) and interprofessional education (IPE) which targets complex team-based care in NIV delivery.Methods and designTwenty hospitals with low baseline rates of NIV use will be randomized to either the OLE or IPE study arm. The primary outcome of the trial is change in the hospital rate of NIV use among patients with COPD requiring ventilatory support. In aim 1, we will compare the uptake change over time of NIV use among patients with COPD in hospitals enrolled in the two arms. In aim 2, we will explore mediators’ role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and implementation effectiveness. Finally, in aim 3, through interviews with providers, we will assess acceptability and feasibility of the educational training.DiscussionsThis study will be among the first to carefully test the impact of IPE in the inpatient setting. This work promises to change practice by offering approaches to facilitate greater uptake of NIV and may generalize to other interventions directed to seriously-ill patients.Trial registrationName of registry: ClinicalTrials.govTrial registration number:NCT04206735Date of Registration: December 20, 2019
BMP4 promotes the metastasis of gastric cancer by inducing epithelial–mesenchymal transition via ID1
Authors: Deng Ganlu , Chen Yihong , Guo Cao , Yin Ling , Han Ying , Li Yiyi , Fu Yaojie , Cai Changjing , Shen Hong , Zeng Shan 
Published: May 2020

ABSTRACT
Epithelial–mesenchymal transition (EMT) is a crucial process for cancer cells to acquire metastatic potential, which primarily causes death in gastric cancer (GC) patients. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β family that plays an indispensable role in human cancers. However, little is known about its roles in GC metastasis. In this study, BMP4 was found to be frequently overexpressed in GC tissues and was correlated with poor patient's prognosis. BMP4 was upregulated in GC cell lines and promoted EMT and metastasis of GC cells both in vitro and in vivo, whereas knockdown of BMP4 significantly inhibited EMT and metastasis of GC cells. Furthermore, the inhibitor of DNA binding 1 (also known as DNA-binding protein inhibitor ID1) was identified as a downstream target of BMP4 using PCR arrays and was upregulated via SMAD1/5/8 phosphorylation. ID1 knockdown attenuated BMP4-induced EMT and invasion in GC cells. Moreover, ID1 overexpression in BMP4 knockdown cells restored the promotion of EMT and cell invasion. In summary, BMP4 induced EMT and promoted GC metastasis by upregulating ID1 expression. Antagonizing BMP4 could be a potential therapeutic strategy for GC metastasis.
OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion
Authors: O'Loughlin Thomas , Kruppa Antonina J. , Ribeiro Andre L. R. , Edgar James R. , Ghannam Abdulaziz , Smith Andrew M. , Buss Folma 
Published: May 2020

ABSTRACT
Optineurin (OPTN) is a multifunctional protein involved in autophagy and secretion, as well as nuclear factor κB (NF-κB) and IRF3 signalling, and OPTN mutations are associated with several human diseases. Here, we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-κB and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations in OPTN linked to primary open-angle glaucoma (POAG) cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. By using proximity labelling proteomics, we identify the linear ubiquitin assembly complex (LUBAC), CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-κB and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment, leading to altered pro-inflammatory cytokine secretion.
A functional in vitro cell-free system for studying DNA repair in isolated nuclei
Authors: Guardamagna Isabella , Bassi Elisabetta , Savio Monica , Perucca Paola , Cazzalini Ornella , Prosperi Ennio , Stivala Lucia A. 
Published: May 2020

ABSTRACT
Assessment of DNA repair is an important endpoint measurement when studying the biochemical mechanisms of the DNA damage response and when investigating the efficacy of chemotherapy, which often uses DNA-damaging compounds. Numerous in vitro methods to biochemically characterize DNA repair mechanisms have been developed so far. However, such methods have some limitations, which are mainly due to the lack of chromatin organization in the DNA templates used. Here we describe a functional cell-free system to study DNA repair synthesis in vitro, using G1-phase nuclei isolated from human cells treated with different genotoxic agents. Upon incubation in the corresponding damage-activated cytosolic extracts, containing biotinylated dUTP, nuclei were able to initiate DNA repair synthesis. The use of specific DNA synthesis inhibitors markedly decreased biotinylated dUTP incorporation, indicating the specificity of the repair response. Exogenously added human recombinant PCNA protein, but not the sensors of UV-DNA damage DDB2 and DDB1, stimulated UVC-induced dUTP incorporation. In contrast, a DDB2PCNA− mutant protein, unable to associate with PCNA, interfered with DNA repair synthesis. Given its responsiveness to different types of DNA lesions, this system offers an additional tool to study DNA repair mechanisms.
This article has an associated First Person interview with the first author of the paper.
Impact of Coronavirus disease (COVID-19) pandemic on health professionals
Authors: Sethi Bilal Ahmed , Sethi Ahsan , Ali Sadaf , Aamir Hira Shireen 
Published: May 2020

Objective: Recognizing the huge potential ramifications of COVID-19 pandemic, this study explores its impact on health professionals personally and professionally along with the associated challenges.
Methods: A descriptive cross-sectional qualitative survey was conducted from March-April 2020. Participants included health professionals from various disciplines in both public and private-sector institutions of Pakistan. The sample size was not predetermined, and an iterative approach of simultaneous data collection and analysis was taken until data and time saturation were reached. Thematic analysis of the qualitative data was carried out by two analysts.
Results: Two hundred and Ninety health professionals responded. They reported an impact on their mental, physical and social well-being. The clinicians mentioned facing an unprecedented workload in overstretched health facilities, while those in academia become engaged with planning/providing emergency remote teaching for the students affecting work-life balance. Some challenges associated with work-from-home and in the hospitals were identified.
Conclusion: During COVID-19, the health professionals are anxious, overworked and financially unstable while planning, creating and caring for others and their families. We need to support them to do their jobs, be safe and stay alive. Future research should explore the fears and coping strategies of health professionals during pandemics.
doi: https://doi.org/10.12669/pjms.36.COVID19-S4.2779
How to cite this:Sethi BA, Sethi A, Ali S, Aamir HS. Impact of Coronavirus disease (COVID-19) pandemic on health professionals. Pak J Med Sci. 2020;36(COVID19-S4):COVID19-S6-S11. doi: https://doi.org/10.12669/pjms.36.COVID19-S4.2779
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.