bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diurnal changes of retinal microvascular circulation and RNFL thickness measured by optical coherence tomography angiography in patients with obstructive sleep apnea–hypopnea
Authors: Cai Yi , Liu Wen-Bo , Zhou Miao , Jin Yu-Tong , Sun Guo-Sheng , Zhao Long , Han Fang , Qu Jin-Feng , Shi Xuan , Zhao Ming-Wei 
Published: August 2022

PurposeTo evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA).MethodsIn this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly.ResultsAfter sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02).ConclusionsThe changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.
Ecological–Health Risk of Antimony and Arsenic in Centella asiatica, Topsoils, and Mangrove Sediments: A Case Study of Peninsular Malaysia
Authors: Yap Chee Kong , Tan Wen Siang , Cheng Wan Hee , Syazwan Wan Mohd , Azrizal-Wahid Noor , Krishnan Kumar , Go Rusea , Nulit Rosimah , Ibrahim Mohd. Hafiz , Mustafa Muskhazli , Omar Hishamuddin , Chew Weiyun , Edward Franklin Berandah , Okamura Hideo , Al-Mutairi Khalid Awadh , Al-Shami Salman Abdo , Sharifinia Moslem , Keshavarzifard Mehrzad , You Chen Feng , Bakhtiari Alireza Riyahi , Bintal Amin , Zakaly Hesham M. H. , Arai Takaomi , Naji Abolfazl , Saleem Muhammad , Abd Rahman Mohd Amiruddin , Ong Ghim Hock , Subramaniam Geetha , Wong Ling Shing 
Published: August 2022

The current study assessed the ecological–health risks of potentially toxic arsenic (As) and antimony (Sb) in the vegetable Centella asiatica, topsoils, and mangrove sediments sampled from Peninsular Malaysia. The As concentrations ranged from 0.21 to 4.33, 0.18 to 1.83, and 1.32 to 20.8 mg/kg dry weight, for the leaves, stems, and roots of the vegetable, respectively. The ranges of Sb concentrations were 0.31–0.62, 0.12–0.35, and 0.64–1.61 mg/kg dry weight, for leaves, stems, and roots of the vegetable, respectively. The children’s target hazard quotient (THQ) values indicated no non-carcinogenic risks of As and Sb in both leaves and stems, although children’s THQ values were higher than those in adults. The calculated values of estimated weekly intake were lower than established provisional tolerable weekly intake of As and Sb for both children and adult consumers. The carcinogenic risk (CR) values of As for children’s intake of leaves and stems of vegetables showed more public concern than those of adults. The levels of Sb and As in the topsoils were generally higher (although not significantly) than those in the mangrove sediments, resulting in a higher geoaccumulation index, contamination factor and ecological risk, hazard index, THQ, and CR values. This indicated that the anthropogenic sources of Sb and As originated from the land-based activities before reaching the mangrove near the coast. The CR of As signifies a dire need for comprehensive ecological–health risks exposure studies, as dietary intake involves more than just vegetable consumption. Therefore, risk management for As and Sb in Malaysia is highly recommended. The present findings of the ecological–health risks of As and Sb based on 2010–2012 samples can be used as an important baseline for future reference and comparison.
Contrasting corn yield responses to nitrogen fertilization in southeast coastal plain soils
Authors: Raza Sajjad , Farmaha Bhupinder Singh 
Published: August 2022

Nitrogen (N) fertilizer recommendations based on yield goals are common and do not consider variability in soil N supply between fields. Nitrogen transformations in soils are dynamic and may vary widely among different soils, climates, cropping systems, and management practices, making it difficult to provide general N recommendation rates for a region, state, or even a county. To optimize N fertilization rates for corn (Zea mays L.), eight field trials were conducted on different fields at the Edisto Research and Education Center of Clemson University in 2018–2021. The soils varied in pH, inorganic N, management practices (irrigate, dryland, cover, and no-cover crop), and climatic conditions (temperature and precipitation). Six nitrogen fertilizer rate treatments were used during 2018 and 2019, eight in 2020, and five in 2021 trials. Test sites were different in each year except in 2021 in which trials were conducted on the same site but were differentiated by multi-species and no-cover crop treatments. Nitrogen fertilizer was applied as a complete one-time dose in all trials in 2018 and 2021 and in several splits in 2019 and 2020. The corn yields generally increased with N fertilization rates; however, a strong variation of up to 4–11 Mg ha−1 existed at each N level among different fields. Based on yield responses, the eight field trials were divided into two groups: low-yielding and high-yielding sites. The low-yielding sites on average produced 3.8 Mg ha−1 of corn, which was 137% less than the corn harvested from high-yielding sites (9.0 Mg ha−1). The agronomic N use efficiency (AgNUE) in high-yielding sites was almost double (32.68 kg kg−1 N) compared to low-yielding sites (17.16 kg kg−1 N), and the differences were even wider for partial factor productivity of N (PFPN). The economic optimum N rate (EONR) remained below 300 kg N ha−1 for all sites with no marked difference among sites. However, relative yield (ratio of corn yield in unfertilized control to the N level giving the highest yield) was comparatively lower in low-yielding sites (29.45%). Baseline inorganic N, pH, and precipitation were identified as the major factors controlling corn yield responses to N fertilization. The yield variations driven by several factors make N management challenging, indicating the need for site-specific N management for corn in the southeast United States.
Conservation status and historical relatedness of South African communal indigenous goat populations using a genome-wide single-nucleotide polymorphism marker
Authors: Chokoe T. C. , Hadebe K. , Muchadeyi F. C. , Nephawe K. A. , Dzomba E. F. , Mphahlele T. D. , Matelele T. C. , Mtileni B. J. 
Published: August 2022

Indigenous goats form the majority of populations in smallholder, low input, low output production systems and are considered an important genetic resource due to their adaptability to different production environments and support of communal farming. Effective population size (Ne), inbreeding levels, and the runs of homozygosity (ROHs) are effective tools for exploring the genetic diversity and understanding the demographic history in efforts to support breeding strategies to use and conserve genetic resources. Across populations, the current Ne of Gauteng was the lowest at 371 animals, while the historical Ne across populations suggests that the ancestor Ne has decreased by 53.86%, 44.58%, 42.16%, and 41.16% in Free State (FS), North West (NW), Limpopo (LP), and Gauteng (GP), respectively, over the last 971 generations. Genomic inbreeding levels related to ancient kinship (FROH &gt; 5 Mb) were highest in FS (0.08 ± 0.09) and lowest in the Eastern Cape (EC) (0.02 ± 0.02). A total of 871 ROH island regions which include important environmental adaptation and hermo-tolerance genes such as IL10RB, IL23A, FGF9, IGF1, EGR1, MTOR, and MAPK3 were identified (occurring in over 20% of the samples) in FS (n = 37), GP (n = 42), and NW (n = 2) populations only. The mean length of ROH across populations was 7.76 Mb and ranged from 1.61 Mb in KwaZulu-Natal (KZN) to 98.05 Mb (GP and NW). The distribution of ROH according to their size showed that the majority (n = 1949) of the detected ROH were &gt; 5 Mb in length compared to the other categories. Assuming two hypothetical ancestral populations, the populations from KZN and LP are revealed, supporting PC 1. The genomes of KZN and LP share a common origin but have substantial admixture from the EC and NW populations. The findings revealed that the occurrence of high Ne and autozygosity varied largely across breeds in communal indigenous goat populations at recent and ancient events when a genome-wide single-nucleotide polymorphism (SNP) marker was used. The use of Illumina goat SNP50K BeadChip shows that there was a migration route of communal indigenous goat populations from the northern part (LP) of South Africa to the eastern areas of the KZN that confirmed their historical relatedness and coincides with the migration periods of the Bantu nation.
“Iron triangle” of regulating the uterine microecology: Endometrial microbiota, immunity and endometrium
Authors: Zhu Na , Yang Xuyan , Liu Qiao , Chen Yahui , Wang Xiaolan , Li Huanhuan , Gao Hong 
Published: August 2022

The uterus is the core place for breeding new life. The balance and imbalance of uterine microecology can directly affect or even dominate the female reproductive health. Emerging data demonstrate that endometrial microbiota, endometrium and immunity play an irreplaceable role in regulating uterine microecology, forming a dynamic iron triangle relationship. Up to nowadays, it remains unclear how the three factors affect and interact with each other, which is also a frontier topic in the emerging field of reproductive tract microecology. From this new perspective, we aim to clarify the relationship and mechanism of the interaction of these three factors, especially their pairwise interactions. Finally, the limitations and future perspectives of the current studies are summarized. In general, these three factors have a dynamic relationship of mutual dependence, promotion and restriction under the physiological or pathological conditions of uterus, among which the regulatory mechanism of microbiota and immunity plays a role of bridge. These findings can provide new insights and measures for the regulation of uterine microecology, the prevention and treatment of endometrial diseases, and the further multi-disciplinary integration between microbiology, immunology and reproductive medicine.
Road testing new CAR design strategies in multiple myeloma
Authors: Rana Priyanka S. , Murphy Elena V. , Kort Jeries , Driscoll James J. 
Published: August 2022

A deeper understanding of basic immunology principles and advances in bioengineering have accelerated the mass production of genetically-reprogrammed T-cells as living drugs to treat human diseases. Autologous and allogeneic cytotoxic T-cells have been weaponized to brandish MHC-independent chimeric antigen receptors (CAR) that specifically engage antigenic regions on tumor cells. Two distinct CAR-based therapeutics designed to target BCMA are now FDA-approved based upon robust, sustained responses in heavily-pretreated multiple myeloma (MM) patients enrolled on the KarMMa and CARTITUDE-1 studies. While promising, CAR T-cells present unique challenges such as antigen escape and T-cell exhaustion. Here, we review novel strategies to design CARs that overcome current limitations. Co-stimulatory signaling regions were added to second-generation CARs to promote IL-2 synthesis, activate T-cells and preclude apoptosis. Third-generation CARs are composed of multiple co-stimulatory signaling units, e.g., CD28, OX40, 4-1BB, to reduce exhaustion. Typically, CAR T-cells incorporate a potent constitutive promoter that maximizes long-term CAR expression but extended CAR activation may also promote T-cell exhaustion. Hypoxia-inducible elements can be incorporated to conditionally drive CAR expression and selectively target MM cells within bone marrow. CAR T-cell survival and activity is further realized by blocking intrinsic regulators of T-cell inactivation. T-Cells Redirected for Universal Cytokine Killing (TRUCKs) bind a specific tumor antigen and produce cytokines to recruit endogenous immune cells. Suicide genes have been engineered into CAR T-cells given the potential for long-term on-target, off-tumor effects. Universal allo-CAR T-cells represent an off-the-shelf source, while logic-gated CAR T-cells are designed to recognize tumor-specific features coupled with Boolean-generated binary gates that then dictate cell-fate decisions. Future generations of CARs should further revitalize immune responses, enhance tumor specificity and reimagine strategies to treat myeloma and other cancers.
Development of a novel score model to predict hyperinflammation in COVID-19 as a forecast of optimal steroid administration timing
Authors: Takeshita Yuichiro , Terada Jiro , Hirasawa Yasutaka , Kinoshita Taku , Tajima Hiroshi , Koshikawa Ken , Kinouchi Toru , Isaka Yuri , Shionoya Yu , Fujikawa Atsushi , Kato Yasuyuki , To Yasuo , Tada Yuji , Tsushima Kenji 
Published: August 2022

ObjectivesThis study aims to create and validate a useful score system predicting the hyper-inflammatory conditions of COVID-19, by comparing it with the modified H-score.MethodsA total of 98 patients with pneumonia (without oxygen therapy) who received initial administration of casirivimab/imdevimab or remdesivir were included in the study. The enrolled patients were divided into two groups: patients who required corticosteroid due to deterioration of pneumonia, assessed by chest X-ray or CT or respiratory failure, and those who did not, and clinical parameters were compared.ResultsSignificant differences were detected in respiratory rate, breaths/min, SpO2, body temperature, AST, LDH, ferritin, and IFN-λ3 between the two groups. Based on the data, we created a corticosteroid requirement score: (1) the duration of symptom onset to treatment initiation ≥ 7 d, (2) the respiratory rate ≥ 22 breaths/min, (3) the SpO2 ≤ 95%, (4) BT ≥ 38.5°C, (5) AST levels ≥ 40 U/L, (6) LDH levels ≥ 340 U/L, (7) ferritin levels ≥ 800 ng/mL, and (8) IFN-λ3 levels ≥ 20 pg/mL. These were set as parameters of the steroid predicting score. Results showed that the area under the curve (AUC) of the steroid predicting score (AUC: 0.792, 95%CI: 0.698–0.886) was significantly higher than that of the modified H-score (AUC: 0.633, 95%CI: 0.502–0.764).ConclusionThe steroid predicting score may be useful to predict the requirement of corticosteroid therapy in patients with COVID-19. The data may provide important information to facilitate a prospective study on a larger scale in this field.
Exploration of combined physical activity and music for patients with Alzheimer’s disease: A systematic review
Authors: Li Kailimi , Cui CanCan , Zhang Haipeng , Jia Luning , Li Rui , Hu Hao-Yu 
Published: August 2022

ObjectiveAlzheimer’s disease (AD) can be treated in different ways, one of which is combined physical activity and music intervention, which is a non-pharmacological one. This study provided a thorough systematic review on the application of combined physical activity and music intervention in patients with AD.MethodOnline sources, such as PubMed, Web of Science, SAGE Premier, EBSCO, and Cochrane, published from January 2002 to March 2022 were searched for articles. Reviewer screened articles on inclusion criteria and identified relevant studies. 200 studies were selected as potentially relevant; of these, eight met all the inclusion criteria.ResultsThe systemic review looked at eight studies, two of which had high methodological quality and six were of moderate quality. Various types of research were included: randomized controlled tails, single-subject study, crossover study, and case report. Music intervention was conducted during an exercise program in six studies. A cognitive stimulation was applied with music therapy and physical activities among two studies. The physical activities or movements included balance training, stretching, strengthening, and different sports activities. Outcome assessment, including the Barthel index in two studies and the functional independence measure, was conducted to evaluate the daily functional score. Mental health was evaluated by Mini-Mental State Examination in three studies.ConclusionCombined physical activity and music intervention are beneficial and improve the cognition, function and well-being of patients with AD. Supporting combined physical and music intervention will play a key role in helping clinical guidelines for both physical therapists and music therapists.
Endovascular treatment for distal basilar artery occlusion stroke
Authors: Song Jiaxing , Yu Zhou , Wang Jian , Luo Xiaojun , Du Jie , Tian Zhengxuan , Yang Shunyu , Xie Weihua , Peng Yuqi , Mu Jinlin , Zi Wenjie , Huang Shuchun , Yang Mei 
Published: August 2022

BackgroundThis study aimed to investigate the clinical outcomes of endovascular treatment (EVT) for distal basilar artery occlusion (BAO) and compare them with the outcomes of standard medical treatment (SMT) in daily clinical practice.MethodsPatients with distal BAO enrolled in the BASILAR study from January 2014 to May 2019 were included. Differences in clinical outcomes were analyzed using Pearson's chi-square test and multivariable logistic regression. Clinical outcomes were evaluated using the modified Rankin Scale (mRS) score at 90 days, the mortality at 90 days, and the occurrence of symptomatic intracranial hemorrhage within 48 h.ResultsAmong the 267 patients with distal BAO (222 patients in the EVT group and 45 patients in the SMT group), compared with the SMT group, the EVT group was associated with a favorable outcome (mRS 0–3; 40.1 vs. 15.6%; aOR 5.44; 95% CI, 1.68–17.66; P = 0.005) and decreased mortality (44.6 vs. 71.1%, aOR 0.32, 95% CI, 0.13–0.77; P = 0.012). In the EVT group, multivariable analysis showed that the initial National Institutes of Health Stroke Scale (NIHSS) score and posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS) were associated with favorable functional outcomes and mortality.ConclusionOur study suggests that, compared with SMT, EVT is technically feasible and safe for patients with distal BAO.
Eculizumab for acute relapse of neuromyelitis optica spectrum disorder: Case report
Authors: Chatterton Sophie , Parratt John Douglas Edward , Ng Karl 
Published: August 2022

IntroductionEculizumab has been shown to be an effective and typically well-tolerated medication in the treatment of neuromyelitis optica spectrum disorder (NMOSD) in maintaining disease remission in patients who are aquaporin-4 water channel autoantibody (AQP4-IgG) seropositive. The efficacy of eculizumab in an acute relapse of NMOSD however is still under review.CaseWe describe a 46 year-old female who presented with acute left monocular vision loss on a background of bilateral optic neuritis treated 15 years prior as suspected NMOSD. She had very poor vision from the right eye (6/60). On presentation she was not on any long-term immunosuppressive agents. Her serum was positive for AQP4-IgG and MRI brain and spine demonstrated areas of demyelination in the corpus callosum and thoracic spine. She was treated with high dose intravenous methylprednisolone and underwent plasmapheresis for five consecutive days, but continued to clinically deteriorate with ongoing blindness in her left eye (light perception only). She was subsequently administered eculizumab with weaning oral corticosteroids. Clinically her vision improved to counting fingers and she remains on maintenance eculizumab infusions in the community. At 3 months, there is a steady improvement but still significant loss of central vision from that eye.ConclusionThe utility of eculizumab in NMOSD may assist with treating acute episodes. This theoretically accords with the mode of action in inhibiting conversion of C5–C5a/b, perhaps arresting the acute inflammatory process in this disease. Given that disease burden and mortality in NMOSD is almost entirely related to relapses, increased use of eculizumab acutely could potentially aid recovery from an attack in very severe attacks, and therefore minimize immediate stepwise accrual of disability.
Superoxide dismutase 2 ameliorates mitochondrial dysfunction in skin fibroblasts of Leber’s hereditary optic neuropathy patients
Authors: Zhou Qingru , Yao Shun , Yang Mingzhu , Guo Qingge , Li Ya , Li Lei , Lei Bo 
Published: August 2022

BackgroundIn Leber’s hereditary optic neuropathy (LHON), mtDNA mutations mediate mitochondrial dysfunction and apoptosis of retinal ganglion cells. Mitochondrial superoxide dismutase 2 (SOD2) is a crucial antioxidase against reactive oxygen species (ROS). This study aims to investigate whether SOD2 could ameliorate mtDNA mutation mediated mitochondrial dysfunction in skin fibroblasts of LHON patients and explore the underlying mechanisms.MethodsThe skin of normal healthy subjects and severe LHON patients harboring m.11778G &gt; A mutation was taken to prepare immortalized skin fibroblast cell lines (control-iFB and LHON-iFB). LHON-iFB cells were transfected with SOD2 plasmid or negative control plasmid, respectively. In addition, human neuroblastoma SH-SY5Y cells and human primary retinal pigmental epithelium (hRPE) cells were stimulated by H2O2 after gene transfection. The oxygen consumption rate (OCR) was measured with a Seahorse extracellular flux analyzer. The level of ATP production, mitochondrial membrane potential, ROS and malondialdehyde (MDA) were measured separately with the corresponding assay kits. The expression level of SOD2, inflammatory cytokines and p-IκBα/IκBα was evaluated by western-blot. Assessment of apoptosis was performed by TUNEL assay.ResultsLHON-iFB exhibited lower OCR, ATP production, mitochondrial membrane potential but higher level of ROS and MDA than control-iFB. Western-blot revealed a significantly increased expression of IL-6 and p-IκBα/IκBα in LHON-iFB. Compared with the negative control, SOD2 overexpression increased OCR, ATP production and elevated mitochondrial membrane potential, but impaired ROS and MDA production. Besides, western-blot demonstrated exogenous SOD2 reduced the protein level of IL-6 and p-IκBα/IκBα. TUNEL assays suggested SOD2 inhibited cells apoptosis. Analogously, in SH-SY5Y and hRPE cells, SOD2 overexpression increased ATP production and mitochondrial membrane potential, but decreased ROS, MDA levels and suppressed apoptosis.ConclusionSOD2 upregulation inhibited cells apoptosis through ameliorating mitochondrial dysfunction and reducing NF-κB associated inflammatory response. This study further support exogenous SOD2 may be a promising therapy for the treatment of LHON.