bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability of the Early Summer Temperature in the Southeastern Tibetan Plateau in Recent Centuries and the Linkage to the Indian Ocean Basin Mode
Authors: Li Jinjian , Jin Liya , Zheng Zeyu , Qin Ningsheng 
Published: April 2022

Abstract
Although many temperature time-series reconstructions, constructed on the basis of tree-ring widths, with lengths of centuries to millennia have been published for many parts of the southeastern Tibetan Plateau (SETP), field reconstruction has been unaddressed to date. Here, we present a tree-ring network comprising 53 chronologies (one δ13C chronology, one regional maximum latewood density chronology, and 51 width chronologies). Using the modified point-by-point reconstruction method, a temperature field consisting of data from 28 meteorological stations in the SETP over the past 200–500 y (the common period was from 1730 to 1998; the longest single period was from 1480 to 2002) was reconstructed. Principal component analysis and rotated principal component analysis results indicated that the reconstructed temperature field may be representative of spatial distribution characteristics. The temperature changes in the SETP were similar. The correlation coefficients between the reconstructed regional average temperature and each observed series were 0.44–0.83 (86% were greater than 0.6, and all the significance tests reported a level of 0.01). Temperature changes were mainly synchronous with those in the middle and low latitudes of the Northern Hemisphere. We then explored the influence of possible climatic forcing and found that the Indian Ocean Basin mode may be a principal factor controlling the interannual variations in the STEP summer temperatures.
Characteristics and Dominant Factors for Natural Fractures in Deep Shale Gas Reservoirs: A Case Study of the Wufeng-Longmaxi Formations in Luzhou Block, Southern China
Authors: Han Lingling , Li Xizhe , Guo Wei , Ju Wei , Cui Yue , Liu Zhaoyi , Qian Chao , Shen Weijun 
Published: April 2022

Abstract
In southern Sichuan Basin, the main production layers are characterized by deeply buried, high stress difference, and complex structural conditions. The Luzhou area is far from large faults, and natural fractures are greatly important for shale gas storage and production. Multi-scale natural fractures control the migration, enrichment, and preservation conditions of shale gas, and facilitate the formation of complex fracture network under the action of hydraulic fracturing. In this study, based on the outcrops, drilling cores, geochemical tests, thin section, and other experiments, the development characteristics of the Wufeng-Longmaxi shale in the Luzhou block, Southern China, are statistically analyzed, and the controlling factors (e.g., tectonic factors, organic matter, mineral components, mechanical properties) are discussed in details. Fractures observed in the outcrops are mainly regional fractures with two groups of orthogonal joints. Similarly, fractures observed in the core are also mainly joints fractures perpendicular to the laminae with three typical features (high-density, high-angle, and unfilled). In detail, steeply dipping fractures (75-90°) account for 78.1% of all fractures, with 85.1% being unfilled, 78.1% having a longitudinal extension less than 4 cm, and 65.1% having a spacing less than 2 cm. In brief, there exist cross-scale similarity among outcrops, cores, and microscopic thin sections, which is critical to the shale gas preservation conditions. Based on this understanding, further research is conducted on the relationship between the fracture density and gas content, which shows that (i) when the fracture density is less than 122 number/m, TOC content and fracture density together positively dominate gas content; (ii) when fracture density exceeds 122 number/m, gas content appears negative with fracture density, and TOC content is not the critical factor anymore. The above study establishes quantitative limits for shale gas preservation in the study block. It may assist in providing references for determining the sweet spot area and further deep shale gas exploration and development in the southern Sichuan Basin.
Clinical Profile and Risk Factors of Central Serous Chorioretinopathy in Al-
Ain, United Arab Emirates
Authors: Jain Manish , Kurian Dhanya , Lal Sarath , Biswas Jyotirmay , Pathak Komal 
Published: April 2022

Background:
Based on the adverse event reporting system, the authors observed unique occupational and pharmacological trends in central serous chorioretinopathy (CSC); despite being a common condition in the region, there are no large epidemiological studies.

Objective:
To describe the clinical profile, risk factors and co-medications of CSC in a multispecialty hospital in UAE.

Methods:
Hospital based retrospective, observational study in which all the confirmed cases of CSC (272) seen between 2010 and 2019 were included. Supplementary data was collected on follow up visits or through telephonic calls.

Results:
The male: female ratio was 17:1; low socio-economic status was (155; 73.45%), and occupations such as drivers (61; 28.9%) and outdoor laborers (59; 27.96%) were the most commonly affected. The majority (78.05%; 185) were single expatriates. Financial worries (105; 50.72%) constituted the leading cause of stress. The usage of corticosteroids (83; 30.51%), nasal decongestants (14.70%) or both (17; 6.25%) within one year was common; mostly (82; 30.14%) for rhinitis/respiratory states, though grossly under-recognized. Muscle relaxants and psychotropic medications were the other major medications used by 24 (8.82%) and 25 (9.19%) cases prior to CSC. Seven of 15 women had at least one condition that alters the endocrinal milieu: Pregnancy (3), recent child birth (1), erratic oral contraceptive intake (1), menopause with liver dysfunction (1), hormone replacement therapy for menopause and endometriosis (1), ovarian cyst and infertility (1) hypothyroidism (3), and Cushing syndrome (1). Chronic/ recurrent forms were seen in 31.08%. There were too few glaucoma patients despite both CSC and glaucoma being common among our patients.

Conclusions:
CSC in Al-Ain predominantly affected males with a specific occupational predisposition. Emotional distress, financial worries, allergic disorders, and endocrinal disorders (among females) were common. Adverse drug events were under-reported compared to the usage of steroid or decongestant users. Suspected pharmacological associations included drugs that modulated the vasomotor tone.
NEAT1: A Novel Long Non-coding RNA Involved in Mediating Type 2 Diabetes and
its Various Complications
Authors: Jia Dengke , He Yaping , Wang Yaqi , Xue Mengzhen , Zhu Leiqi , Xia Fangqi , Li Yuanyang , Gao Yan , Li Luoying , Chen Silong , Xu Guangfu , Yuan Chengfu 
Published: April 2022

Background:
Nuclear‐enriched abundant transcript 1 (abbreviated as NEAT1) is a long-chain noncoding
RNA involved in various physiological and pathological processes. This study aimed to clarify the
effect and molecule system of NEAT1 within non-alcoholic fatty liver disease (NAFLD) as well as type 2 diabetes
(T2DM).

Method:
In this review, current studies concerning mechanisms of NEAT1l, in the development of type 2 diabetes
and its complications have been summarized and analyzed. Also, we searched the papers based on
NEAT1 related to NAFLD. The related studies were obtained through a systematic search of Pubmed.

Results:
NEAT1 displays a close correlation with how T2DM occurs and develops, and it was confirmed to be
significantly up-regulated in T2DM and its various complications (e.g., diabetics nephropathy, diabetics cardiomyopathy,
diabetics retinopathy as well as diabetic neuropathy). Besides, NEAT1 is capable of impacting the
occurrence, development and prognosis of NAFLD and T2DM.

Conclusion:
LncRNA NEAT1 is likely to act as a novel therapeutic target for T2DM and its complications.
Moreover, non-alcoholic fatty liver disease is also correlated with NEAT1.
Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based
Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp
Authors: Murali Mahadevamurthy , Gowtham Hittanahallikoppal Gajendramurthy , Ansari Mohammad Azam , Alomary Mohammad N. , Alghamdi Saad , Almehmadi Mazen , Singh Sudarshana Brijesh , Shilpa Natarajamurthy , Aiyaz Mohammed , Kalegowda Nataraj , Ledesma Ana E. , Amruthesh Kestur Nagaraj 
Published: April 2022

Background:
Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality rate and infecting people worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders.

Objective:
The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and perform the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of potential compounds.

Methods:
Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform.

Results:
A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/ mol. Among these, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-D-galactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs.

Conclusion:
The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.
The Role of Bone Morphogenetic Protein 4 in Lung Diseases
Authors: Dong Xiaoxiao , Mao Yimin , Gao Pengfei 
Published: April 2022

:
Bone morphogenetic protein 4 (BMP4) is a multifunctional secretory protein
that belongs to the transforming growth factor β superfamily. BMPs transduce their
signaling to the cytoplasm by binding to membrane receptors of the serine/threonine
kinase family, including BMP type I and type II receptors. BMP4 participates in various
biological processes, such as embryonic development, epithelial-mesenchymal
transition, and maintenance of tissue homeostasis. The interaction between BMP4 and
the corresponding endogenous antagonists plays a key role in the precise regulation of
BMP4 signaling. In this paper, we review the pathogenesis of BMP4-related lung
diseases and the foundation on which BMP4 endogenous antagonists have been
developed as potential targets.
Microhomology-Mediated Break-Induced Replication: A Possible
Molecular Mechanism of the Formation of a Large CNV in FBN1
Gene in a Patient with Marfan Syndrome
Authors: Buki Gergely , Hadzsiev Kinga , Bene Judit 
Published: April 2022

Background:
Marfan syndrome (MFS) is an autosomal dominant multisystem
disorder caused by mutations in the fibrillin-1 gene (FBN1). A small portion of them is
copy number variations (CNVs), which can occur through recombination-based,
replication-based mechanisms or retrotransposition. Not many have been characterized
precisely in MFS.

Methods:
A female patient with suspected Marfan syndrome was referred for genetic
testing at our institute. After systematic sequencing of FBN1, TGFBR1, and TGFBR2
genes, multiplex ligation-dependent probe amplification was applied. Long-range PCR,
subsequent Sanger sequencing with designed primers, and preliminary in silico analysis
were applied for the precise characterization of the breakpoints.

Results:
Primary analysis displayed a de novo large deletion affecting exons 46 and 47
in the FBN1 gene, which resulted in the loss of the 31st and 32nd calcium-binding EGFlike
domains. Further examination of the breakpoints showed a 4916 nucleotide long
deletion localized in intronic regions. Surprisingly a ‘TG’ dinucleotide insertion was
detected at the junction. We hypothesize that the CNV formation was generated by a
rare event based on the known microhomology-mediated break-induced replication
(MMBIR).

Conclusion:
An increasing number of CNVs are associated with Mendelian diseases
and other traits. Approximately 2-7% of the cases in MFS are caused by CNVs. Up to
date, hardly any model was proposed to demonstrate the formation of these genomic
rearrangements in the FBN1 gene. Hereby, with the help of previous models and
breakpoint analysis, we presented a potential mechanism (based on MMBIR) in the
formation of this large deletion.
Resistance of Lenvatinib in Hepatocellular Carcinoma
Authors: Xu Qiuran , Huang Dongsheng , Guo Jinhui , Zhao Junjun 
Published: April 2022

Abstract:
Lenvatinib is a multikinase inhibitor which mainly hinders liver cancer proliferation by inhibiting
angiogenesis. In 2018, Lenvatinib was approved for the first-line treatment of patients with advanced
hepatocellular carcinoma [HCC] in the United States, the European Union, Japan, and China.
Lenvatinib has been established as a sorafenib replacement drug with a higher objective response rate
[ORR], longer progression-free survival [PFS], and time to progression [TTP]. Lenvatinib resistance
during hepatocellular carcinoma treatment has become increasingly common in recent years. Accordingly,
it is necessary to determine factors associated with Lenvatinib resistance and explore solutions. In
this review, we sought to explore the drug resistance mechanisms of Lenvatinib in liver cancer and
methods to reduce drug resistance and summarized the recent achievements of Lenvatinib in liver cancer
treatment.
An Eight-year, Single-center Experience on Ultrasound Assisted Thrombolysis
with Moderate-dose, Slow-infusion Regimen in Pulmonary Embolism
Authors: Kaymaz Cihangir , Akbal Ozgur Yasar , Keskin Berhan , Tokgoz Hacer Ceren , Hakgor Aykun , Karagoz Ali , Tanyeri Seda , Kultursay Barkın , Kulahcioglu Seyhmus , Dogan Cem , Bayram Zubeyde , Efe Süleyman Çağan , Erkılınç Atakan , Tanboga Ibrahim Halil , Akbulut Mehmet , Ozdemir Nihal , Tapson Victor , Konstantinides Stavros 
Published: April 2022

Background:
There is limited data on moderate-dose with slow-infusion thrombolytic regimen
by ultrasound-asssisted-thrombolysis (USAT) in patients with acute pulmonary embolism (PE).

Aim:
In this study, our eight-year experience on USAT with moderate-dose, slow-infusion tissue-type
plasminogen activator (t-PA) regimen in patients with PE at intermediate-high- and high-risk was presented,
and short-, and long-term effectiveness and safety outcomes were evaluated.

Methods:
Our study is based on the retrospective evaluation of 225 patients with PE having multiple
comorbidities who underwent USAT.

Results:
High- and intermediate-high-risk were noted in 14.7% and in 85.3% of patients, respectively.
Mean t-PA dosage was 35.4±13.3 mg, and the infusion duration was 26.6±7.7 h. Measures of pulmonary
artery (PA) obstruction and right ventricle (RV) dysfunction were improved within days (p<0.0001
for all). During the hospital stay, major and minor bleeding and mortality rates were 6.2%, 12.4%, and
6.2%, respectively. Bleeding and unresolved PE accounted for 50% and 42.8% of in-hospital mortality,
respectively. Age, rate, and duration of t-PA were not associated with in-hospital major bleeding and
mortality. Oxygen saturation exceeded 90% in 91.2% of patients at discharge. During follow-up of median
962 (610-1894) days, high-risk status related to 30-day mortality, whereas age >65 years was associated
with long-term mortality.

Conclusions:
Our real-life experience with USAT with moderate-dose, slow-infusion t-PA regimen in
patients with PE at high-and intermediate-high risk demonstrated clinically relevant improvements in
PA obstructive burden and RV dysfunction. Age, rate or infusion duration of t-PA was not related to
major bleeding or mortality risk, whereas unresolved obstruction remained as a lethal issue.
Determinants and Incidence of Chronic Kidney Disease with Tenofovir-
Based Antiretroviral Therapy Regimens: A Cohort Study in HIV-Infected
Adults in South China
Authors: Liu Fang , Huang Jin-Song , Bao Jian-Feng , Wang Yi , Liu Hong , Chen Chen , Miao Liang-Bin , Li Zhao-Yi , Wang Miao-Chan 
Published: April 2022

Background:
The data of the impact of tenofovir (TDF) on kidney damage in Chinese
HIV-1 infected patients are limited.

Objective:
The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease
(CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients
starting with a TDF-based regimen.

Method:
We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions
were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m2 during follow-up) and RKFD
(eGFR decline > 10 mL/min/1.73 m2/year). A linear mixed-effects model was used to quantify the
average eGFR change per 48 weeks. A generalized estimating equation regression analysis was
conducted to determine the risk factors associated with renal dysfunction. The method of multiple
imputations was used to reduce the bias caused by missing data.

Results:
In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals
experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up
period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59
mL/min/1.73 m2 before 48 weeks to -17.61 mL/min/1.73 m2 after 288 weeks. For every 10
mL/min/1.73 m2 increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each
10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased
to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively.
Anemia and higher viral load were significantly associated with RKFD. The results were robust
across a range of multiple imputation analyses.

Conclusions:
TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed
patients are more likely to have renal dysfunction, especially those with older age, anemia, lower
baseline eGFR, and higher viral load.
Analysis of Membrane Proteins of Streptomycin-Resistant Mycobacterium
tuberculosis Isolates
Authors: Bisht Deepa , Singh Rananjay , Sharma Devesh , Sharma Divakar , Gupta Mahendra Kumar 
Published: April 2022

Background:
Drug-resistant tuberculosis remains a health security threat and resistance
to second-line drugs limits the options for treatment. Consequently, there is an utmost need for identifying
and characterizing new biomarkers/drug targets of prime importance. Membrane proteins
have an anticipated role in biological processes and could qualify as biomarkers/drug targets. Streptomycin
(SM) is recommended as a second-line treatment regimen only when amikacin resistance
has been confirmed. As extensively drug-resistant (XDR) isolates are frequently cross-resistant to
second-line injectable drugs, an untapped potential for the continued use of SM has been suggested.

Objective:
The study aimed to analyze the membrane proteins overexpressed in SM resistant isolates
of Mycobacterium tuberculosis using proteomics approaches.

Methods:
Membrane proteins were extracted employing sonication and ultracentrifugation. Twodimensional
gel electrophoresis (2DGE) of membrane proteins was performed and identification of
proteins was done by liquid chromatography-mass spectrometry (LCMS) and bioinformatics tools.

Results:
On analyzing the two-dimensional (2D) gels, five protein spots were found overexpressed
in the membrane of SM resistant isolates. Docking analysis revealed that SM might bind to the conserved
domain of overexpressed proteins and Group-based prediction system-prokaryotic ubiquitinlike
protein (GPS-PUP) predicted potential pupylation sites within them.

Conclusion:
These proteins might be of diagnostic importance for detecting the cases early and for
exploring effective control strategies against drug-resistant tuberculosis, particularly SM.
The Role of Ultrasound in Evaluating the Effect of Urate-lowering Drugs
in Gout Patients
Authors: El-Mallah Reem , Ibrahim Rehab Ali , El Attar Enas A. 
Published: April 2022

Background:
Gout is one of the most common inflammatory arthritis, where identifica-tion of MSU crystals in synovial fluid is a widely used diagnostic measure. Ultrasonography has a great sensitivity in detecting signs of MSU deposits, such as tophi and double contour (DC), as mentioned in the latest gout criteria, allowing early clinical diagnosis and therapy.

Objective:
The objective of this study was to evaluate the changes in ultrasound of gout patients’ knee and 1st metatarsophalangeal joint (MTP1) after initiation of urate-lowering therapy (ULT) drugs in the six-month period.

Methods:
Forty-three patients, fulfilling the ACR/EULAR 2015 criteria of gout with a score of >8, were enrolled; they were in between attacks and not on ULT for the last 6 months, or SUA concen-tration (SUA) of >6.0 mg/dL. Full examination, evaluation of joints pain by visual analog scale (VAS), ultrasonography (US) for tophus and DC at the knee, and MTP1 were performed at baseline and at 3 and 6 months (M3, M6) after starting ULT.

Result:
After 6 months of treatment, patients reached the target SUA level showed higher disap-pearance of DC sign (p<0.05) and a decrease in tophus size (p<0.05). The percentage of tophus size at 6th month was 26.4% and 3% for DC sign disappearance, which was more at MTP1.

Conclusion:
Ultrasound examination in screening for gout tophi or DC sign before starting ULT and during follow-up is important and complements clinical examination.