bluuebunny/crossref_metadata_2025_split huggingface dataset:
Niemann–Pick disease type C in Palestine: genotype and phenotype of sixteen patients and report of a novel mutation in the NPC1 gene
Authors: Dweikat Imad , Thaher Othman , Abosleem Abdulrahman , Zeer Almotazbellah , Mokh Ameer Abo 
Published: September 2021

Abstract
Background
Niemann–Pick disease type C (NPC) is an autosomal recessive, neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in these genes are associated with abnormal endosomal–lysosomal trafficking, resulting in the accumulation of tissue-specific lipids in lysosomes.

Methods
We described sixteen patients with NPC diagnosed between the age of 1 month and 30 years at two tertiary care centers in Palestine. The clinical phenotype, brain magnetic resonance imaging (MRI), and molecular genetic analysis data were reviewed.

Results
The diagnosis was confirmed by molecular analysis in all patients. Fourteen out of sixteen patients were homozygous for the NPC1 p.G992W variant. Among them, most were categorized as having the late-infantile neurological form of disease onset. They predominantly manifested with early-onset visceral manifestations in the form of hepatosplenomegaly and prolonged neonatal jaundice, and late-onset neuropsychiatric manifestations in the form of vertical supranuclear gaze palsy (VSGP), ataxia, cognitive impairment and seizures. Brain MRI in 6 patients was normal in 5 or consistent with cerebellar hemisphere atrophy in 1 of them. Two other mutations were identified in the NPC1 gene, of which p.V845Cfs*24 was novel.

Conclusions
Our results revealed phenotypic heterogeneity of NPC even within the same genotype, and add to the increasingly recognized evidence that cholestatic jaundice and hepatosplenomegaly during infancy, should alert the physician for the possibility of NPC. We reported a novel mutation in the NPC1 gene further expanding its genotype.
The effective function of circular RNA in colorectal cancer
Authors: Ameli-Mojarad Mandana , Ameli-Mojarad Melika , Hadizadeh Mahrooyeh , Young Chris , Babini Hosna , Nazemalhosseini-Mojarad Ehsan , Bonab Maziar Ashrafian 
Published: September 2021

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.
Accuracy of SD Malaria Ag P.f/Pan® as a rapid diagnostic test in French Amazonia
Authors: Pujo Jean Marc , Houcke Stéphanie , Lemmonier Sarah , Portecop Patrick , Frémery Alexis , Blanchet Denis , Djossou Felix , Kallel Hatem , Demar Magalie 
Published: September 2021

Abstract
Background
French Guiana (FG) is a French overseas territory where malaria is endemic. The current incidence rate is 0.74‰ inhabitants, and Plasmodium vivax is widely predominating even though Plasmodium falciparum is still present due to imported cases mainly from Africa. In FG, rapid diagnostic test (SD Malaria Ag P.f/Pan®) is based on the detection of pan-pLDH, PfHRP2, and PfHRP3 antigens, while in South America, the share of deletion of PfHRP2 gene is significantly increasing. Accordingly, the study questions the reliability of RDTs in the Amazonian context.

Methods
The study is retrospective. It is conducted over 4 years and analysed 12,880 rapid diagnostic tests (RDTs) compared to concomitant Blood Film Tests (BFTs) sampled for malaria diagnosis.

Results
The global assessment of the accuracy of SD Malaria Ag P.f/Pan® in the diagnostic of malaria shows both Positive and Negative Predictive Values (PPV and NPV) higher than 95%, except for PPV in the diagnosis of malaria to P. falciparum (88%). Overall, the concordance rate between RDT and BFT (positive/positive; negative/negative) was 99.5%. The PPV of the RDT in the follow-up of patients diagnosed with P. falciparum was the lowest during the first 28 days. The PPV of the RDT in the follow-up of patients diagnosed with P. vivax was the lowest during the first 21 days. The global sensitivity of SD Malaria Ag P.f/Pan® test was, on average, 96% (88.2–100) for P. falciparum and 93% (90.6–94.2) for P. vivax. The global specificity was 99.8% (99.5–100) for all included species.

Conclusion
SD Malaria Ag P.f/Pan® is a reliable rapid test used for the first-line diagnosis in remote healthcare centres. The test results should be interpreted in the light of patient’s recent medical history and the date of arrival to FG.
In search of the last malaria cases: ethnographic methods for community and private-sector engagement in malaria elimination in Vietnam, Laos, and Cambodia
Authors: Masunaga Yoriko , Muela Ribera Joan , Nguyen Thuan Thi , Tesfazghi Kemi , Peeters Grietens Koen 
Published: September 2021

Abstract
Background
Despite significant strides made in reducing malaria morbidity and mortality in the Greater Mekong Subregion, malaria transmission continues amongst the most ‘hard-to-reach’, such as forest-goers and mobile and migrant populations, who face access obstacles to malaria diagnosis and treatment. As such, regional malaria elimination strategies endeavour to incorporate the private sector and local communities in improving surveillance and detection of the last malaria cases in remote forested areas. The question remains, however, whether such strategies can reach these hard-to-reach populations and effectively reduce their disproportionate burden of malaria. This paper evaluates the strategy of community and private sector engagement in a malaria elimination project in Vietnam, Laos, and Cambodia.

Methods
Ethnographic research, incorporating in-depth interviews, participant observations with informal discussions, and group discussions were conducted in Bu Gia Map commune, Binh Phuc province of Vietnam; in Phouvong district, Attapeu province of Laos; and, in nine newly established and informal communities in the provinces of Mondul Kiri, Steung Treng, Kratie, Kampong Thom, and Prah Vihear of Cambodia.

Results
Different types of factors limited or enhanced the effectiveness of the participatory approaches in the different settings. In Vietnam, inter-ethnic tensions and sensitivity around forest-work negatively affected local population’s health-seeking behaviour and consequent uptake of malaria testing and treatment. In Laos, the location of the project collaborative pharmacies in the district-centre were a mismatch for reaching hard-to-reach populations in remote villages. In Cambodia, the strategy of recruiting community malaria-workers, elected by the community members, did manage to reach the remote forested areas where people visited or stayed.

Conclusions
‘Hard-to-reach’ populations remain hard to reach without proper research identifying the socio-economic-political environment and the key dynamics determining uptake in involved communities and populations. Solid implementation research with a strong ethnographic component is required to tailor malaria elimination strategies to local contexts.
Mixture toxicity, cumulative risk, and environmental justice in United States federal policy, 1980–2016
Authors: Sprinkle Robert Hunt , Payne-Sturges Devon C. 
Published: September 2021

AbstractToxic chemicals — “toxicants” — have been studied and regulated as single entities, and, carcinogens aside, almost all toxicants, single or mixed and however altered, have been thought harmless in very low doses or very weak concentrations. Yet much work in recent decades has shown that toxicants can injure wildlife, laboratory animals, and humans following exposures previously expected to be harmless. Additional work has shown that toxicants can act not only individually and cumulatively but also collectively and even synergistically and that they affect disadvantaged communities inordinately — and therefore, as argued by reformers, unjustly. As late as December 2016, the last full month before the inauguration of a president promising to rescind major environmental regulations, the United States federal environmental-health establishment, as led by the Environmental Protection Agency (EPA), had not developed coherent strategies to mitigate such risks, to alert the public to their plausibility, or to advise leadership in government and industry about their implications. To understand why, we examined archival materials, reviewed online databases, read internal industry communications, and interviewed experts. We confirmed that external constraints, statutory and judicial, had been in place prior to EPA’s earliest interest in mixture toxicity, but we found no overt effort, certainly no successful effort, to loosen those constraints. We also found internal constraints: concerns that fully committing to the study of complex mixtures involving numerous toxicants would lead to methodological drift within the toxicological community and that trying to act on insights from such study could lead only to regulatory futility. Interaction of these constraints, external and internal, shielded the EPA by circumscribing its responsibilities and by impeding movement toward paradigmatic adjustment, but it also perpetuated scientifically dubious policies, such as those limiting the evaluation of commercial chemical formulations, including pesticide formulations, to only those ingredients said by their manufacturers to be active. In this context, regulators’ disregard of synergism contrasted irreconcilably with biocide manufacturers’ understanding that synergism enhanced lethality and patentability. In the end, an effective national response to mixture toxicity, cumulative risk, and environmental injustice did not emerge. In parallel, though, the National Institute of Environmental Health Sciences, which was less constrained, pursued with scientific investigation what the EPA had not pursued with regulatory action.
Improving the estimation of alpine grassland fractional vegetation cover using optimized algorithms and multi-dimensional features
Authors: Lin Xingchen , Chen Jianjun , Lou Peiqing , Yi Shuhua , Qin Yu , You Haotian , Han Xiaowen 
Published: September 2021

Abstract
Background
Fractional vegetation cover (FVC) is an important basic parameter for the quantitative monitoring of the alpine grassland ecosystem on the Qinghai-Tibetan Plateau. Based on unmanned aerial vehicle (UAV) acquisition of measured data and matching it with satellite remote sensing images at the pixel scale, the proper selection of driving data and inversion algorithms can be determined and is crucial for generating high-precision alpine grassland FVC products.

Methods
This study presents estimations of alpine grassland FVC using optimized algorithms and multi-dimensional features. The multi-dimensional feature set (using original spectral bands, 22 vegetation indices, and topographical factors) was constructed from many sources of information, then the optimal feature subset was determined based on different feature selection algorithms as the driving data for optimized machine learning algorithms. Finally, the inversion accuracy, sensitivity to sample size, and computational efficiency of the four machine learning algorithms were evaluated.

Results
(1) The random forest (RF) algorithm (R2: 0.861, RMSE: 9.5%) performed the best for FVC inversion among the four machine learning algorithms driven by the four typical vegetation indices. (2) Compared with the four typical vegetation indices, using multi-dimensional feature sets as driving data obviously improved the FVC inversion accuracy of the four machine learning algorithms (R2 of the RF algorithm increased to 0.890). (3) Among the three variable selection algorithms (Boruta, sequential forward selection [SFS], and permutation importance-recursive feature elimination [PI-RFE]), the constructed PI-RFE feature selection algorithm had the best dimensionality reduction effect on the multi-dimensional feature set. (4) The hyper-parameter optimization of the machine learning algorithms and feature selection of the multi-dimensional feature set further improved FVC inversion accuracy (R2: 0.917 and RMSE: 7.9% in the optimized RF algorithm).

Conclusion
This study provides a highly precise, optimized algorithm with an optimal multi-dimensional feature set for FVC inversion, which is vital for the quantitative monitoring of the ecological environment of alpine grassland.
Organizational contextual factors that predict success of a quality improvement collaborative approach to enhance integrated HIV-tuberculosis services: a sub-study of the Scaling up TB/HIV Integration trial
Authors: Gengiah Santhanalakshmi , Connolly Catherine , Yende-Zuma Nonhlanhla , Barker Pierre M. , Nunn Andrew J. , Padayatchi Nesri , Taylor Myra , Loveday Marian , Naidoo Kogieleum 
Published: September 2021

Abstract
Background
A quality improvement (QI) collaborative approach to enhancing integrated HIV-Tuberculosis (TB) services may be effective in scaling up and improving the quality of service delivery. Little is known of the role of organizational contextual factors (OCFs) in influencing the success of QI collaboratives. This study aims to determine which OCFs were associated with improvement in a QI collaborative intervention to enhance integrated HIV-TB services delivery.

Methods
This is a nested sub-study embedded in a cluster-randomized controlled trial. Sixteen nurse supervisors (clusters) overseeing 40 clinics were randomized (1:1) to receive QI training and mentorship, or standard of care support (SOC). In the QI arm, eight nurse supervisors and 20 clinics formed a “collaborative” which aimed to improve HIV-TB process indicators, namely HIV testing, TB screening, isoniazid preventive therapy (IPT) initiations, viral load testing, and antiretroviral therapy for TB patients. OCFs measured at baseline were physical infrastructure, key staff, flexibility of clinic hours, monitoring data for improvement (MDI), and leadership support. Surveys were administered to clinic staff at baseline and month 12 to assess perceptions of supportiveness of contexts for change, and clinic organization for delivering integrated HIV-TB services. Linear mixed modelling was used to test for associations between OCFs and HIV-TB process indicators.

Results
A total of 209 clinic staff participated in the study; 97 (46.4%) and 112 (53.6%) from QI and SOC arms, respectively. There were no differences between the QI and SOC arms scores achieved for physical infrastructure (78.9% vs 64.7%; p = 0.058), key staff (95.8 vs 92; p = 0.270), clinic hours (66.9 vs 65.5; p = 0.900), MDI (63.3 vs 65; p = 0.875, leadership support (46.0 vs 57.4; p = 0.265), and perceptions of supportiveness of contexts for change (76.2 vs 79.7; p = 0.128 and clinic organization for delivering integrated HIV-TB services (74.1 vs 80.1; p = 0.916). IPT initiation was the only indicator that was significantly improved in the parent study. MDI was a significantly associated with increasing IPT initiation rates [beta coefficient (β) = 0.004; p = 0.004].

Discussion
MDI is a practice that should be fostered in public health facilities to increase the likelihood of success of future QI collaboratives to improve HIV-TB service delivery.

Trial registration
Clinicaltrials.gov, NCT02654613. Registered 01 June 2015.
Treatment outcome and compliance to dose-intensified linac-based SBRT for unfavorable prostate tumors using a novel real-time organ-motion tracking
Authors: Lucchini Raffaella , Panizza Denis , Colciago Riccardo Ray , Vernier Veronica , Daniotti Martina Camilla , Faccenda Valeria , Arcangeli Stefano 
Published: September 2021

Abstract
Purpose/objectives
To report preliminary data on treatment outcome and compliance to dose-intensified organ sparing SBRT for prostate cancer using a novel electromagnetic transmitter-based tracking system (RayPilot® System) to account for intra-fractional organ motion.

Material/methods
Thirteen patients with intermediate unfavorable (9) and selected high-risk (4) prostate cancer underwent dose-escalated SBRT in 4 or 5 fractions (BED1.5 = 279 Gy and 253 Gy, respectively). The VMAT treatment consisted in two 6FFF or 10FFF full arcs optimized to have the 95% isodose covering at least 95% of the PTV (2 mm isotropic expansion of the CTV). Whenever the real-time tracking registered a displacement that exceeded 2 mm during the setup and/or the beam delivery, the treatment was interrupted and the prostate motion was promptly corrected. The incidence of treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity, patient QoL and PSA outcomes were computed from the start of treatment to the last follow-up date.

Results
All patients completed the treatment in the expected time (10.2 +/− 4.2 minutes) and their compliance to the procedure was excellent. No clinically significant acute Grade 2 or higher GI (rectal) and GU side effects were observed within 90 days from the treatment completion. The median IPSS increased from 8 at baseline to 12 one-month after treatment and settled to 6 at 3 months. EPIC-26 scores in the urinary domain decreased from a median baseline of 86 pre-treatment to 79 at one-month and returned to baseline at a later timepoint (median score of 85 at 3 months). EPIC-26 scores in the bowel domains did not show significant changes within 3 months following RT. The prostate was found within 1 mm from its initial position in 78% of the beam-on time, between 1 and 2 mm in 20%, and exceeded 2 mm only in 2%, after correction for motion which was performed in 45% of the fractions, either during setup or beam delivery.

Conclusions
Our preliminary findings show that dose intensified SBRT for unfavorable prostate tumors does not come at the cost of an increased toxicity, provided that a reliable technique for real time prostate monitoring is ensured. Fast FFF beams contributed to reduce intra-fractional motion. These observations need to be confirmed on a larger scale and a longer follow up.
Comparing the running subcuticular technique versus the Donati technique in open carpal tunnel release: a randomized controlled trial
Authors: Suwannaphisit Sitthiphong , Aonsong Wachirakorn , Suwanno Porames , Yuenyongviwat Varah 
Published: September 2021

Abstract
Background
There are various skin suture techniques for wound closure following carpal tunnel release, and well-performed suturing will result in low post-operative scar tenderness. The aim of this study was to compare the Donati suture technique and running subcuticular technique in terms of surgical scar, post-operative pain and functional outcome in open carpal tunnel release.

Methods
One-hundred forty-two patients were randomized using a computer-generated random number table into two groups receiving either running subcuticular suturing or Donati suturing after surgical intervention. We evaluated postoperative scarring using the Patient and Observer Scar Assessment Scale (POSAS), pain intensity using a verbal numerical rating scale, and functional outcomes using the Thai version of the Boston Carpal Tunnel Questionnaire after surgical decompression for carpal tunnel syndrome at 2, 6, and 12 weeks. Continuous data are reported as mean ± SD while normally distributed or as median (interquartile range) when the distribution was skewed.

Results
Lower scores at 2 weeks were given by the patients receiving the running subcuticular suture technique than the Donati suture technique (15.3 ± 4.8 vs 17 ± 4.6, respectively, P < 0.05) while the observer scores were not significantly different (15.6 ± 5.8 vs 16.7 ± 5.2, respectively, P = 0.15). At both 6 and 12 weeks post-surgical decompression both patient and observer scores were not significantly different. There were no differences between the groups in terms of VNRS pain scores and functional Boston Carpal Tunnel Scores at all time points.

Conclusions
This randomized controlled trial found that although scarring assessments were slightly better in the earliest period following wound closure after surgical decompression in carpal tunnel syndrome using the running subcuticular suture, the final results at 3 months postoperative were not significantly different.

Trial registration
The study was registered at https://www.thaiclinicaltrials.org/ (TCTR20191204002).
Changes of lake organic carbon sinks from closed basins since the Last Glacial Maximum and quantitative evaluation of human impacts
Authors: Li Yu , Zhang Xinzhong , Xu Lingmei , Zhang Yuxin , Ye Wangting , Li Yichan 
Published: September 2021

Abstract
Background
Closed basins occupy 21% of the world’s land area and can substantially affect global carbon budgets. Conventional understanding suggests that the terminal areas of closed basins collect water and carbon from throughout the entire basin, and changes in lake organic carbon sinks are indicative of basin-wide organic carbon storages. However, this hypothesis lacks regional and global validation. Here, we first validate the depositional process of organic carbon in a typical closed-basin region of northwest China using organic geochemical proxies of both soil and lake sediments. Then we estimate the organic carbon sinks and human impacts in extant closed-basin lakes since the Last Glacial Maximum (LGM).

Results
Results show that 80.56 Pg organic carbon is stored in extant closed-basin lakes mainly found in the northern mid-latitudes. Carbon accumulation rates vary from 17.54 g C m−2 yr−1 during modern times, 6.36 g C m−2 yr−1 during the mid-Holocene and 2.25 g C m−2 yr−1 during the LGM. Then, we evaluated the influence by human activities during the late Holocene (in the past three thousand years). The ratio of human impacts on lake organic carbon storage in above closed basins is estimated to be 22.79%, and human-induced soil organic carbon emissions in the past three thousand years amounted to 207 Pg.

Conclusions
While the magnitude of carbon storage is not comparable to those in peatland, vegetation and soil, lake organic carbon sinks from closed basins are significant to long-term terrestrial carbon budget and contain information of climate change and human impact from the whole basins. These observations improve our understanding of carbon sinks in closed basins at various time scales, and provide a basis for the future mitigation policies to global climate change.