bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management and control of schistosomiasis in Agusan del Sur, Philippines: A modeling study
Authors: Riñon Jayrah Bena E. , Mendoza Renier , V Aurelio A. de los Reyes , Belizario Vicente Y. , Mendoza Victoria May P. 
Published: March 2022

Abstract

Schistosomiasis is a neglected tropical disease endemic in the Philippines, affecting 28 provinces in 12 regions. This parasitic disease is caused by Schistosoma japonicum, a zoonotic parasite that infects other mammalian hosts aside from humans. In this study, a mathematical model is developed to describe the transmission of schistosomiasis in Agusan del Sur, Philippines and investigate control strategies that could lead to possible elimination of the disease. The model considers humans as definitive hosts, carabaos as reservoir hosts, and snails as intermediate hosts. Available schistosomiasis data from the Philippine Department of Health are utilized to estimate the transmission probability, contact rate between snails and humans, and infectivity from humans and carabaos to snails. Various intervention measures in mitigating the disease are explored under the framework of optimal control theory. The strategies include efforts to increase treatment coverage and compliance of mass drug administration; efforts to reduce humans and snails contacts by providing access to latrines and clean water, improving hygiene practices, targeted mollusciciding, etc.; and efforts to reduce carabaos and snails contact by using mechanized tractors. Results highlight the significance of an integrated approach and prioritizing control strategies considering resource constraints.
A phase I study of C-CAR088, a novel humanized anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma
Authors: Qu Xiaoyan , An Gang , Sui Weiwei , Wang Tingyu , Zhang Xian , Yang Junfang , Zhang Yan , Zhang Lu , Zhu Dan , Huang Jiaqi , Zhu Shigui , Yao Xin , Li Jing , Zheng Chengxiao , Zhu Kevin , Wei Yutiang , Lv Xiaoteng , Lan Liping , Yao Yihong , Zhou Daobin , Lu Peihua , Qiu Lugui , Li Jianyong 
Published: March 2022

Abstract
BackgroundAnti-B-cell maturation antigen (BCMA) chimeric antigen receptor-T cell (CAR T) therapy shows remarkable efficacy in patients with relapsed or refractory multiple myeloma (RRMM). C-CAR088, a novel second-generation humanized anti-BCMA CAR T cell therapy, was developed. MethodsThis phase I dose-escalation and expansion study assessed the safety and efficacy of three dosages of C-CAR088 in patients with RRMM. As of July 2, 2021, 31 patients had been infused with C-CAR088. ResultsAny grade cytokine release syndrome (CRS) developed in 29 patients (93.5%), and grade 3 CRS occurred in three patients (9.7%). One patient from the high-dose group (4.5-6.0 × 106 CAR T cells/kg) developed grade 1 neurotoxicity. No dose-limiting toxicities were observed in any dose group, and all adverse events were reversible after proper management. The overall response, stringent complete response, complete response (CR), and very good partial response rates were 96.4%, 46.4%, 10.7%, and 32.1%, respectively. The CR rate in the medium-dose (3.0 × 106 CAR T cells/kg) and high-dose (4.5-6.0 × 106 CAR T cells/kg) groups was 54.5% and 71.4%, respectively. In the CR group, 15 (93.7%) patients achieved minimal residual disease (MRD) negativity (test sensitivity >1/10-5). All seven patients with double-hit or triple-hit multiple myeloma achieved MRD-negative CR. ConclusionsOur findings demonstrate the manageable safety profile and potential efficacy of C-CAR088.Trial registrationNCT03815383 was registered in December 2018.NCT03751293 was retrospectively registered in May 2019.NCT04295018 was registered in October 2019. NCT04322292 was registered in March 2020.
TCERG1L Hypermethylation Is A Risk Factor Of Diabetic Retinopathy In Chinese Children With Type 1 Diabetes
Authors: Qian Yu , Xiao Ying , Lin Qiurong , Xiang Zhaoyu , Cui Lipu , Sun Jiaqi , Li Sicong , Qin Xinran , Jin Peiyao , Yang Chenhao , Zou Haidong 
Published: March 2022

Abstract
Background: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children.Methods/Results: This study consists of two surveys. 40 T1DM children with no DR participated in the first survey. Their DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay. Comparison of the methylation patterns was made between participants with macular retinal thinning (cases) and the others (controls). The second survey included 27 T1DM children, among which 4 had DR. Pyrosequencing was used to validate the results of the 850K array, and the methylation patterns of four DMS was compared between participants with and without DR.In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|> 0.1 and Adj.P-value <0.05), while 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypometh­ylated in the case group relative to the controls. Four of the identified DMS with a potential role in diabetes were chosen to be validated in the second survey. Pyrosequencing revealed that the TCERG1L (cg07684215) gene was hypermethylated in the four T1DM children with DR (p=0.018), which was consistent with the result from the first survey. The methylation status of PDXK, PARK2 and PPARG showed no difference (all p>0.05) between participants with and without DR.Conclusions: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.
Severe burn injury caused by carbon monoxide poisoning: two case reports
Authors: Hu Delin , Jiang Wei , Liu Chun , Song Junhui , Meng Chengying , Lu Shiping , Hu Jiayan , Zhou Yan , Zhou Shunying , Yu Youxin , Sun Yexiang 
Published: March 2022

Abstract
CO poisoning is the most common cause of injuries and deaths after poisoning worldwide. Exposed charcoals and furnaces are often used for heating in parts of world. When CO poisoning occurs in a coma, people may faint on burning charcoal and furnace, and suffer severe burns. This article reports two cases of severe burns caused by CO poisoning, and the first patient even required amputation of his left leg. Besides, the long and painful treatments and irreversible changes in appearance and function have brought huge economic pressure and serious psychological barriers to patients. Therefore, education and prevention of CO poisoning are indeed worthy of attention.
The outcome of linezolid induced optic and peripheral neuropathy in a Pakistani patient treated for multidrug-resistant pulmonary tuberculosis: A case report
Authors: Nawaz Ahmad 
Published: March 2022

Abstract
Linezolid is a core second-line drug used for the treatment of extensively and multidrug-resistant tuberculosis. Linezolid showed the promised efficacy in the treatment of drugs resistant tuberculosis. However, the associated adverse effects such as optic and peripheral neuropathy are the major obstacles for its long-term therapy. We recently encountered a case of progressive deterioration of vision and numbness in the feet in a 32-years-old male undergoing linezolid therapy for 12 months for multidrug-resistant tuberculosis. Nerve conduction studies were highly suggestive of sensory polyneuropathy while the fundoscopic image was highly favorable of optic neuropathy. A slight improvement was seen in vision with no improvement or worsening of peripheral neuropathy on follow-up visits after the discontinuation of linezolid. In a developing country like Pakistan, whereas the management of developing resistance to tuberculosis is a major problem, awareness among physicians for close follow-up of a patient using long-term linezolid therapy should be created to avoid such serious optic and peripheral neuropathy.
Lncrna HOXD-AS1 Functions As A Cerna To Promote Hepatocellular Carcinoma Metastasis In Zebrafish Xenograft Models
Authors: Zhang Ying , Wang Xiao-Lu , Qin Feng , Jia Shao-Chang 
Published: March 2022

Abstract
Recent studies have suggested that long noncoding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) plays an important role in hepatocellular carcinoma (HCC) metastasis as a competing endogenous RNA (ceRNA). However, there is no in vivo evidence supporting this. Employing zebrafish HCC xenograft as an in vivo metastasis model, we aim to verify the role of ceRNA network of HOXD-AS1 in HCC metastasis. The quantitative reverse transcription PCR (qRT-PCR) assay was used to assess the expression level of HOXD-AS1 in HCC cell lines. Knockdown of HOXD-AS1 or miR-130a-3p was performed by transfecting small interfering RNA (siRNA) or microRNA (miRNA) inhibitor, respectively. The proliferation and migration of HCC cells in vitro were analyzed by CCK-8 and transwell assays. The growth and metastasis of HCC cells in vivo were assessed by zebrafish xenograft models. We verified that HOXD-AS1 was overexpressed in all tested HCC cell lines compared to the normal hepatic cells. Silence of HOXD-AS1 suppressed cell proliferation and migration in Hep3B and Huh7 HCC cell lines, respectively. In zebrafish xenograft models, knockdown of HOXD-AS1 also reduced the growth and metastasis of the two HCC cells. Downregulation of miR-130a-3p rescued the metastasis which inhibited by silence of HOXD-AS1 in vitro and in vivo. Moreover, HOXD-AS1 knockdown enhanced the inhibition effect of oxaliplatin for HCC progression in vitro and in vivo. Our study demonstrates the pro-metastastic role of the HOXD-AS1/miR-130a-3p ceRNA network in HCC cells, and provides evidence that HOXD-AS1 may serve as a biomarker and potential therapeutic target for HCC metastasis.
Does selection occur at the intermediate zone of two insufficiently isolated populations? A whole-genome analysis along an altitudinal gradient
Authors: Yoshida Naofumi , Morinaga Shin-Ichi , Wakamiya Takeshi , Ishii Yuu , Kubota Shosei , Hikosaka Kouki 
Published: March 2022

Abstract
Adaptive divergence would occur even between the insufficiently isolated populations when there is a great difference in the environments between their habitats. The individuals present in the intermediate zone of the two divergent populations are expected to have an admixed genetic structure due to gene flow. A selective pressure that acts on the genetically admixed individuals may limit the gene flow and promote the adaptive divergence. Here, we addressed a question whether the selection occurs in the genetically admixed individuals between the divergent populations and assessed its effects on the population divergence. We obtained the whole-genome sequences of a perennial montane plant, Arabidopsis halleri, which has clear phenotypic dimorphisms between altitudes, along an altitudinal gradient of 359–1,317 m with a high spatial resolution (mean altitudinal interval of 20 m). We found the zone where the highland and lowland genes were mixing (intermediate subpopulation). We sought genetic variants that had been selected in the intermediate subpopulation. In the intermediate subpopulation, we identified 9 and 22 genetic regions, which included 7 and 19 genes, had a high frequency of alleles that are accumulated in highland and lowland subpopulations, respectively, suggesting that these genes have been selected in the admixed zone. This selection might limit the gene flow and contribute to the adaptive divergence along the altitudes. We also identified a genetic region that contains different alleles from those in both highland and lowland subpopulations, though the variants were not included in encoded genes. We also identified 7 genetic regions had low heterozygote frequencies in the intermediate subpopulation. We could not find any genetic regions whose heterozygote frequency was higher than theoretical expectation. We conclude that different types of selection in addition to gene flow occur at the intermediate altitude and shape the genetic structure across altitudes.
Spatio-Temporal Control of THz Emission
Authors: Huang Hsin-hui , Juodkazis Saulius , Gamaly Eugene , Nagashima Takeshi , Yonezawa Tetsu , Hatanaka Koji 
Published: March 2022

Abstract
Polarization fine control of THz emission is demonstrated with a tilted micro-thin water flow by the irradiation of two cross-linearly-polarized femtosecond laser pulses (800 nm, 35 fs, transform-limited) with spatio-temporal offsets. With an optimized horizontal offset at ∼ 11 𝜇m between the ∼ 8 𝜇m focal spots and time delay at 4.7 ns, circularly-polarized THz emission was obtained with its intensity enhancement more than 1,500-times if compared with the single pulse irradiation. It is shown that the photon-number-based efficiency from the laser to THz at 7.1x10^−3 is achieved with the optimisation of the double pulse irradiation. Polarization-resolved THz time-domain spectroscopy and time-resolved shadowgraphy imaging revealed that the circularly-polarized THz emission originates from the focal volume in front of the water flow. Coupling between a shockwave due to air-breakdown and water ablation-mediated mass transport by the first pulse with a laser wake-field along the optical path of the main pulse is responsible for the point-like single-cycle THz source.
HIP Fracture REhabilitation Program for older adults with hip fracture (HIP-REP) based on Activity of Daily Living: a feasibility study
Authors: Røpke Alice , Morville Anne-Le , Møller Trine Elleby , Delkus Emma Cæcilie Guttzeit , Juhl Carsten Bogh 
Published: March 2022

Abstract
Background: A Rehabilitation Program for older adults with hip fracture (HIP-REP) based on Activity of Daily Living has been developed.Objectives: Assessing the feasibility and safety of the HIP-REP program to inform a future randomized controlled trial (RCT).Design: Feasibility study inspired by the Complex-intervention development (Medical Research Council framework phase II)Setting: Cross sectoral including Copenhagen University Hospital, Herlev and Gentofte and rehabilitation centers in Herlev, Gentofte and Lyngby-Taarbæk municipalities.Participants: Eighteen older adults (above 65 years) with hip fracture were recruited from the orthopedic wards.Intervention: A cross-sectoral rehabilitation intervention was tailored to the needs of older adults with hip fracture highlighting systematic goal setting and strategies focused on activities of daily living.Measurements: Pre-defined feasibility criteria: participants recruitment and retention, duration of measuring the outcome, adherence to intervention, and adverse events, along with self-reported outcomes and an objective measurement of performance in activity of daily living.Results: Recruitment rate was 4.5/month. Outcome measures were performed but length and number of questionnaires were a burden. Thirteen out of eighteen participants completed the study three dropped out and two died. Adherence among the 13 was 100%. Focus group revealed issues regarding coordinating the intervention, ensuring procedural processes across sectors regarding recruitment of participants, and documentation in the database. Participants expressed satisfaction with the intervention and felt safe during intervention. Assessment of Motor and Process Skills showed better increase between (range 0.4 to 1.6) in ADL motor ability measures and better increase between (range 0.4 to 0.7) for process ability. No clear association between outcome improvements and intervention adherence.Conclusions:The cross-sectoral intervention based on daily activities was feasible and safe for older adults with hip fracture. A future RCT, with an improved recruitment strategy and reduced number of outcome measures will evaluate the effectiveness in improving independence and safety performance of activity of daily living.Trial registration: ClinicalTrials.gov ID: NCT03828240
Mapping Nutrition Interventions in Guatemala To Identify Opportunities to Improve Coverage and Coordination
Authors: Asturias Gabriela , Cordon Ana , Pineda Estuardo , Figueroa Alice , Zhang Xian , Proaño Gabriela V , Jimenez Elizabeth Yakes , Rohloff Peter 
Published: March 2022

Abstract
Background
Guatemala has one of the highest rates of chronic child malnutrition (stunting) in the world, with minimal improvements over time, despite intensifying efforts. In 2018, a mapping effort was conducted with nutrition stakeholders, modelled after similar successful efforts in other countries.
Methods
A public-private consortium used a survey to collect information from non-governmental nutrition stakeholders in Guatemala, including institutional name, sector, geographic areas of activities, and types of activities implemented. The survey data were used to populate an online mapping tool (ArcGIS Online). The distribution of institutions and programmatic activities at the departmental level was compared to child stunting prevalence using heat maps and linear regression. Geographic distribution of nutrition-specific and nutrition-sensitive activities aligning with Guatemala's four national strategy pillars (primary care services; education and behavior change; water sanitation and hygiene; and household income generation) were examined.
Results
5,861 program activities from 99 institutions were mapped. The majority of institutions were national non-governmental, community-based, or private sector organizations. Heat maps and statistical analysis demonstrated some misalignment between the distribution of resources versus national strategy priority areas and nutrition need. There were a low number of education and behavior change activities at a national level and relatively few primary care and health-sector strengthening activities in some priority departments.
Conclusions
Mapping stakeholder institutions and nutrition activities in Guatemala identified several areas where resource allocation could be optimized to better address child stunting. The mapping initiative has been incorporated into Guatemala's national planning process and can assist with future monitoring efforts.
Preparation and In Vitro Evaluation of Thermosensitive Liposomes Targeting Ovarian Cancer
Authors: Pu Ximing , Wang Xingming , Wang Fang , Li Sixie , Yin Guangfu 
Published: March 2022

Introduction:
Liposomes have been widely used in drug delivery systems because the encapsulation
of liposomes changes the biological distribution profile and improves the therapeutic indices of
various drugs. Thermosensitive liposomes have been proven to be a precise and effective method for
cancer therapy in many preclinical studies. However, the lack of specific targeting ability to cancer cells
limited their application in safe and efficient chemotherapy.

Materials and Methods:
In the present study, an ovarian targeting ligand namely WSGFPGVWGASVK (WSG)
screened by phage display in vivo was grafted on the thermosensitive phospholipids to prepare the liposomes
targeting ovarian cancer cells. WSG was first grafted onto the hydrophilic terminal of DSPEPEG2000
molecules, and then the WSG modified thermosensitive liposomes (WSG-Lipo) were prepared
by thin-film hydration method. Doxorubicin hydrochloride (DOX) was used as a model drug to investigate
the drug release behavior of liposomes at different temperatures. The specificity of liposomes to
SKOV-3 cells was studied by cell uptake in vitro.

Results:
The WSG-Lipo-DOX could release more DOX at 42°C than at 37°C, showing stronger specificity
to SKOV-3 cells and thus selectively inhibiting SKOV-3 cells activity in vitro.

Conclusion:
The active targeting liposome showed potential in improving the specificity of thermosensitive
liposomes and would be applied in the chemotherapy combined with a thermotherapy.
Development of Biocompatible Nanoparticles of Tizanidine Hydrochloride in Orodispersible Films: In vitro Characterization, Ex vivo Permeation, and Cytotoxic Study on Carcinoma Cells
Authors: Dutt Rohit , Kaushik Deepak , Sinha Suhani , Thapa Sonia , Singh Shashank , Verma Ravinder , Pandey Parijat , Mittal Vineet , Rahman Md. Habibur 
Published: March 2022

Background:The main limitations of the therapeutic effectiveness of tizanidine hydrochloride (TNZ) are its low bioavailability due to its tendency to undergo first-pass metabolism and short biological half-life. These factors make it an ideal candidate for formulating orally disintegrating films.Objective:The present study was aimed to prepare nanoparticles of tizanidine hydrochloride using biodegradable polymers and loading them on orodispersible films to obtain a sustained release dissolution profile with improved permeability and further study the cytotoxicity on A549 lung carcinoma cells, MCF7 breast cancer cells, and HOP 92 non-small lung adenocarcinoma cells.Methods:The fast-dissolving film of TNZ HCl was prepared by the solvent-casting method and characterized using scanning electron microscopy, FTIR, and XRD, and evaluated for critical quality attributes for this type of dosage form such as disintegration time, tensile strength, drug content, dissolution, and ex vivo permeability. In vitro cytotoxicity studies were also conducted on cancer cell lines to confirm the cytotoxic effect.Results:The polymeric matrix containing the drug provided a rapid disintegration time varying between 7±2 and 30±2 seconds, adequate tensile strength between 1.4 and 11.25 N/mm2, and improved permeability through porcine buccal mucosa when compared to the reference product.Conclusion:A study of the cytotoxic effect on the MCF-7 breast cancer cells and A549 lung carcinoma cells revealed that tizanidine hydrochloride nanoparticles at 2.3 mg/film exhibited an IC50 value of 65.1 % cytotoxicity on MCF-7, approximately 100% on HOP92, and 83.5 % on A549 lung carcinoma cells, thus paving the way for a new paradigm of research for a cytotoxic study on MCF-7, HOP92, and A549 cell lines using the subject drug model prepared as oral films or biodegradable nanoparticles in oral films for site-specific targeting.
Summary of Probiotic Potential of the Kefir for the Prevention and
Alleviation of Functional GI Diseases
Authors: Malik Taqdees , Naz Sheikh Saba 
Published: March 2022

Background:
Functional Gastrointestinal (GI) disease is a term that refers to a range
of disease conditions involving chronic diarrhea, irritable bowel syndrome, constipation,
inflammatory bowel disease (IBD), and lactose intolerance. Statistical reports have documented
>40% of the world's population is being afflicted by functional GI disorders. Consequences of
frequent intake of antibiotics include mortality of gut microflora, antibiotic-associated diarrhea,
the establishment of antibiotic resistance, and inference with healthy bodily functions. To
overcome the harms of antibiotics, studies are being conducted to determine the potential of
probiotics as alternatives to antibiotics.

Aim of Study:
The purpose of constructing this literature review is to outline the potential
attributes of Kefir and to assess the solitary efficiency of this beverage in the amelioration of GI
disease conditions.

Methodology:
Extraction of data entailed digging of literature hubs including PubMed, PubMed
Central, Research Gate, Science Direct, and Google Scholar, employing a different combination
of keywords to retrieve substantial details. Selection criteria of the articles involved the
published reports of preceding 10 years (2012-2021) that exhibited relevancy with the topic

Conclusion:
Kefir grains having different origins provide a distinct array of antimicrobial
spectrums and are found to be effective against different pathogens. IBDs, diarrheal sicknesses,
and constipation can be alleviated by the consumption of this beverage. Moreover, the probioticantibiotic combination is also essential for the mitigation of several diseases. The synergistic
impact of several microbial strains is vital for the treatment of celiac disease. Lactose maldigestion can be relieved by the consumption of kefir having β-galactosidase enzyme activity.