bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of the literature on the impact of the Seguro Popular
Authors: Colchero M. A. , Gómez R. , Bautista-Arredondo S. 
Published: April 2022

Abstract
Background
The Seguro Popular (SP) was launched in 2004 to increase access to healthcare and reduce catastrophic expenditures among the Mexican population. To document the evidence on its effectiveness, we conducted a systematic review of impact evaluations of the SP.

Methods
We included papers using rigorous quasi-experimental designs to assess the effectiveness of the SP. We evaluated the quality of each study and presented the statistical significance of the effects by outcome category.

Results
We identified 26 papers that met the inclusion criteria. Sixteen studies that evaluated the impact of SP on financial protection found consistent and statistically significant positive effects in 55% of the 65 outcomes analyzed. Nine studies evaluating utilization of health services for the general and infant populations found effectiveness on 40% of 30 outcomes analyzed. Concerning screening services for hypertension, diabetes, and cervical and prostate cancer, we found three studies evaluating 14 outcomes and finding significant effects on 50% of them. Studies looking at the impact of SP on diabetes, hypertension, and general health care and treatment evaluated 19 outcomes and found effects on 21% of them. One study assessed five diabetes monitoring services and found positive effects on four of them. The only study on morbidity and mortality found positive results on three of the four outcomes of interest.

Conclusion
We found mixed evidence on the impact of SP on financial protection, healthcare utilization, morbidity and mortality. In the 26 studies included in this review, researchers found positive effects in roughly half of the outcomes and null results on the rest.
XGBoost-based and tumor-immune characterized gene signature for the prediction of metastatic status in breast cancer
Authors: Li Qingqing , Yang Hui , Wang Peipei , Liu Xiaocen , Lv Kun , Ye Mingquan 
Published: April 2022

Abstract
Background
For a long time, breast cancer has been a leading cancer diagnosed in women worldwide, and approximately 90% of cancer-related deaths are caused by metastasis. For this reason, finding new biomarkers related to metastasis is an urgent task to predict the metastatic status of breast cancer and provide new therapeutic targets.

Methods
In this research, an efficient model of eXtreme Gradient Boosting (XGBoost) optimized by a grid search algorithm is established to realize auxiliary identification of metastatic breast tumors based on gene expression. Estimated by ten-fold cross-validation, the optimized XGBoost classifier can achieve an overall higher mean AUC of 0.82 compared to other classifiers such as DT, SVM, KNN, LR, and RF.

Results
A novel 6-gene signature (SQSTM1, GDF9, LINC01125, PTGS2, GVINP1, and TMEM64) was selected by feature importance ranking and a series of in vitro experiments were conducted to verify the potential role of each biomarker. In general, the effects of SQSTM in tumor cells are assigned as a risk factor, while the effects of the other 5 genes (GDF9, LINC01125, PTGS2, GVINP1, and TMEM64) in immune cells are assigned as protective factors.

Conclusions
Our findings will allow for a more accurate prediction of the metastatic status of breast cancer and will benefit the mining of breast cancer metastasis-related biomarkers.
Ethnomedicinal landscape: distribution of used medicinal plant species in Nepal
Authors: Kunwar Ripu M. , Baral Bikash , Luintel Sanjeev , Uprety Yadav , Poudel Ram C. , Adhikari Binaya , Adhikari Yagya P. , Subedi Suresh C. , Subedi Chandra K. , Poudel Prakash , Paudel Hem R. , Paudel Basanta , Kunwar Laxmi Mahat , Upadhayaya Kul S. , Bhattarai Shandesh , Pyakurel Dipesh , Kutal Durga H. , Pandey Pramod , Bhandari Ananta , Thapa Gokarna J. , Zambrana Narel Y. Paniagua , Bussmann Rainer W. 
Published: April 2022

Abstract
Background
The risk of losing traditional knowledge of medicinal plants and their use and conservation is very high. Documenting knowledge on distribution and use of medicinal plants by different ethnic groups and at spatial scale on a single platform is important from a conservation planning and management perspective. The sustainable use, continuous practice, and safeguarding of traditional knowledge are essential. Communication of such knowledge among scientists and policy makers at local and global level is equally important, as the available information at present is limited and scattered in Nepal.

Methods
In this paper, we aimed to address these shortcomings by cataloguing medicinal plants used by indigenous ethnic groups in Nepal through a systematic review of over 275 pertinent publications published between 1975 and July 2021. The review was complemented by field visits made in 21 districts. We determined the ethnomedicinal plants hotspots across the country and depicted them in heatmaps.

Results
The heatmaps show spatial hotspots and sites of poor ethnomedicinal plant use documentation, which is useful for evaluating the interaction of geographical and ethnobotanical variables. Mid-hills and mountainous areas of Nepal hold the highest number of medicinal plant species in use, which could be possibly associated with the presence of higher human population and diverse ethnic groups in these areas.

Conclusion
Given the increasing concern about losing medicinal plants due to changing ecological, social, and climatic conditions, the results of this paper may be important for better understanding of how medicinal plants in use are distributed across the country and often linked to specific ethnic groups.
Intrathecal morphine in combination with bupivacaine as pre-emptive analgesia in posterior lumbar fusion surgery: a retrospective cohort study
Authors: Trivedi R. , John J. , Ghodke A. , Trivedi J. , Munigangaiah S. , Dheerendra S. , Balain B. , Ockendon M. , Kuiper J. 
Published: April 2022

Abstract
Background
The purpose of this study was to evaluate the efficacy of intrathecal morphine (ITM) in combination with bupivacaine as pre-emptive analgesia in patients undergoing posterior lumbar fusion surgery. This is in comparison with traditional opioid analgesics such as intravenous (IV) morphine.

Methods
Two groups were identified retrospectively. The first (ITM group) included patients who had general anaesthesia (GA) with low-dose spinal anaesthesia prior to induction using 1–4 mls of 0.25% bupivacaine and 0.2 mg ITM. 1 ml of 0.25% bupivacaine was administered per hour of predicted surgery time, up to a maximum of 4 ml. The insertion level for the spinal anaesthetic corresponded to the spinal level of the iliac crest line and the level at which the spinal cord terminated. The control group had GA without any spinal anaesthesia. Patients were instead administered opioid analgesia in the form of IV morphine or diamorphine. The primary outcome was the consumption of opioids administered intraoperatively and in recovery, and over the first 48 h following discharge from the post-anaesthesia care unit (PACU). Total opioid dose was measured, and a morphine equivalent dose was calculated. Secondary outcomes included visual analogue scale (VAS) pain scores in recovery and at day two postoperatively, and the length of stay in hospital.

Results
For the ITM group, the median total amount of IV morphine equivalent administered intraoperatively and in recovery, was 0 mg versus 17 mg. The median total amount morphine equivalent, administered over the first 48 h following discharge from PACU was 20 mg versus 80 mg. Both are in comparison with the control group. The median length of stay was over 1 day less and the median VAS for pain in recovery was 6 points lower. No evidence was found for a difference in the worst VAS for pain at day two postoperatively.

Conclusion
ITM in combination with bupivacaine results in a significantly decreased use of perioperative opioids. In addition, length of hospital stay is reduced and so too is patient perceived pain intensity.
Trial registration The study was approved by the ethics committee at The Robert Jones and Agnes Hunt Orthopaedic Hospital as a service improvement project (Approval no. 1617_004).
Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats
Authors: Gao Hongru , Tong Xiaoyu , Hu Wei , Wang Yicong , Lee Kuinyu , Xu Xiaoqing , Shi Jiemei , Pei Zhenle , Lu Wenhan , Chen Yuning , Zhang Ruonan , Wang Zheyi , Wang Ziyu , Han Chengzhi , Wang Yu , Feng Yi 
Published: April 2022

AbstractBackgroundLow-frequency electroacupuncture (EA) has been shown to ameliorate obesity and reproductive dysfunctions in patients with polycystic ovary syndrome (PCOS), and further explorations in PCOS-like rats showed that EA could affect white adipose tissue. However, the function and neuromodulation of brown adipose tissue (BAT) in PCOS and after EA treatment have remained unknown. The present study focused on the role of BAT in PCOS-like rats and its relationship with EA and characterized the three-dimensional (3D) innervation of BAT associated with activation molecules.MethodsFemale rats (21 days old) were implanted with dihydrotestosterone or fed with a high fat diet to establish PCOS-like and obesity models, respectively, and then EA treatment at “Guilai” (ST 29) and “Sanyinjiao” (SP 6) was carried out for 4 weeks. In the present study, morphological analysis, 3D imaging, molecular biology, and other experimental techniques were used to study the sympathetic nerves and activity of BAT.ResultsPCOS-like rats showed both obvious weight gain and reproductive dysfunction, similar to what was seen in obese rats except for the absence of reproductive dysfunction. The body weight gain was mainly caused by an increase in white adipose tissue, and there was an abnormal decrease in BAT. Because both the lipid metabolism and reproductive disorders could be improved with bilateral EA at “Guilai” (ST 29) and “Sanyinjiao” (SP 6), especially the restoration of BAT, we further investigated the neuromodulation and inflammation in BAT and identified the sympathetic marker tyrosine hydroxylase as one of the key factors of sympathetic nerves. Modified adipo-clearing technology and 3D high-resolution imaging showed that crooked or dispersed sympathetic nerves, but not the twisted vasculature, were reconstructed and associated with the activation of BAT and are likely to be the functional target for EA treatment.ConclusionOur study highlights the significant role of BAT and its sympathetic innervations in PCOS and in EA therapy.
Identifying patients with Lynch syndrome using a universal tumor screening program in an integrated healthcare system
Authors: Crain Philip R. , Zepp Jamilyn M. , Gille Sara , Jenkins Lindsay , Kauffman Tia L. , Shuster Elizabeth , Goddard Katrina A.B. , Wilfond Benjamin S. , Hunter Jessica Ezzell 
Published: April 2022

Abstract
Introduction
Lynch syndrome (LS) is associated with an increased risk of colorectal (CRC) and endometrial (EC) cancers. Universal tumor screening (UTS) of all individuals diagnosed with CRC and EC is recommended to increase identification of LS. Kaiser Permanente Northwest (KPNW) implemented a UTS program for LS among individuals newly diagnosed with CRC in January 2016 and EC in November 2016. UTS at KPNW begins with immunohistochemistry (IHC) of tumor tissue to determine loss of mismatch repair proteins associated with LS (MLH1, MSH2, MSH6, and PMS2)., IHC showing loss of MLH1 is followed by reflex testing (automatic testing) to detect the presence of the BRAF V600E variant (in cases of CRC) and MLH1 promoter hypermethylation to rule out likely sporadic cases.

Materials and methods
Individuals newly diagnosed with CRC and EC were identified between the initiation of the respective UTS programs and July 2018. Electronic medical records were reviewed to extract patient data related to UTS, including IHC and reflex testing results, date of referrals to the genetics department, and results of germline genetic testing for LS.

Results
313 out of 362 individuals diagnosed with CRC and 61 out of 64 individuals diagnosed with EC who were eligible were screened by IHC for LS. Most (47/52 or 90%, including 46/49 CRC and 1/3 EC) individuals that were not screened by IHC only had a biopsy sample available. Fourteen individuals (3.7% overall, including 13/313 CRC and 1/61 EC) received an abnormal result after reflex testing and were referred for genetic counseling. Of these, 10 individuals (71% overall, including 9/13 CRC and 1/1 EC) underwent germline genetic testing for LS. Five individuals diagnosed with CRC were found to have pathogenic variants. in PMS2 (n = 3), MLH1 (n = 1), and MSH6 (n = 1). No pathogenic variants were identified in individuals diagnosed with EC.

Conclusions
UTS identified individuals at risk for LS. Most individuals who screened positive for LS had follow-up germline genetic testing for LS. The consistent use of biopsy samples is an opportunity to improve UTS.
Inertial effects due to eruption-induced atmospheric disturbances identified by superconducting gravimeter observations at Matsushiro, Japan
Authors: Imanishi Yuichi 
Published: April 2022

AbstractThe violent eruption of Hunga Tonga-Hunga Ha’apai volcano on January 15, 2022 induced strong atmospheric disturbances, which traveled around the world as atmospheric Lamb waves. When this wave passed through the superconducting gravimeter station at Matsushiro, Japan, a large signal of gravity changes was recorded. Also, barometers installed around Matsushiro recorded wave trains of pressure changes. Analysis of the barometer data revealed that the atmospheric disturbances traveled as plane waves. Applying the theory of atmospheric loading for traveling plane waves, the observed gravity changes were well reproduced by a sum of three components of atmospheric loading, namely, Newtonian, free-air and inertial effects. In particular, the inertial effect of atmospheric loading, which is rarely observed, was clearly identified in the gravity data. From the theoretical modeling, an estimate of rigidity in the shallow region of the Earth was also obtained.
Graphic Abstract
Four cases of gastric adenocarcinoma and proximal polyposis of the stomach treated by robotic total gastrectomy
Authors: Iwakawa Yosuke , Yoshikawa Kozo , Okamoto Koichi , Takayama Tetsuji , Tokunaga Takuya , Nakao Toshihiro , Nishi Masaaki , Takasu Chie , Kashihara Hideya , Wada Yuma , Yoshimoto Toshiaki , Yamashita Shoko , Shimada Mitsuo 
Published: April 2022

Abstract
Background
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare disease and characterized by a unique point mutation in the promoter 1B region of the adenomatous polyposis coli (APC) gene. There are two aims in surgery for GAPPS; the first is prophylactic gastrectomy, and the second is excising concurrent cancer. We performed robotic total gastrectomy (RTG) for four cases of GAPPS.

Case presentation
Case 1 was a woman in her 40 s whose sister had died from gastric cancer. Mutational analysis revealed mutation of APC exon 1B. We performed prophylactic gastrectomy. Case 2 was a woman in her 30 s who had a mutation of APC exon 1B, and preoperative biopsy revealed suspected adenocarcinoma. Case 3 was a woman in her 40 s who was diagnosed with gastric cancer with multiple polyps in the stomach and a mutation of APC exon 1B. Case 4 was a woman in her 20 s in whom biopsy revealed low-grade dysplasia of a raised lesion. She had a mutation in APC exon 1B. We performed RTG with D1 + lymphadenectomy in all patients, and there were no intraoperative complications.

Conclusions
Patients with GAPPS are mainly followed regularly with repeat biopsy, and tumors are detected in an early stage. As the safety of robotic surgery for the early gastric cancer is reported, RTG is an option for these patients. This is the first report of RTG for GAPPS patients.
Proton beam therapy causing pericarditis – a rare case of radiation induced cardiotoxicity
Authors: Gupta Rahul , Lin Muling , Freedman Gary M. , Sundlof Deborah W. , Fadlon Cheri Silverstein 
Published: April 2022

AbstractAcute pericarditis is caused by the inflammation of the pericardium which can result in an effusion around the heart. Proton beam therapy causing radiation-induced pericarditis is not a well-known cause of pericarditis. We present a case of a patient with Li-Fraumeni Syndrome who developed acute onset pericarditis, presumed to be secondary to proton beam therapy.
Screening and biocontrol evaluation of indigenous native Trichoderma spp. against early blight disease and their field assessment to alleviate natural infection
Authors: Imran Muhammad , Abo-Elyousr Kamal A. M. , Mousa Magdi A. , Saad Maged M. 
Published: April 2022

Abstract
Background
Early blight disease of tomato caused by pathogenic fungi Alternaria solani is the most significant and common disease throughout the world as well as in Kingdom of Saudi Arabia. The aim of this study was to isolate and identify native Trichoderma species from the Jeddah region in Saudi Arabia; evaluate their antagonistic potential against A. solani; and study their influence early blight disease severity in greenhouse and in open field.

Results
The present study focused to explore the biocontrolling potential of native Trichoderma spp. against A. solani strain to compare with a conventional fungicide. Out of 21, 3 Trichoderma isolates showed an antifungal activity and significantly inhibited the mycelial growth of pathogen that were identified as Trichoderma atroviride, T. harzianum and T. longibrachiatum by their ITS region sequence analysis. Strong in vitro mycelial growth suppression (70.66%) was also recorded at 400 ppm Mancozeb (90%WP®) fungicide. Further, these Trichoderma bioagents and fungicide were further evaluated in greenhouse (artificially inoculated) and in field on naturally infected tomato plants. In greenhouse, (13.74%) disease severity after T. harzianum treatment was recorded, followed by T. longibrachiatum (25.83%) and T. atroviride (21.67%). The disease severity after fungicide (50 mg/L; 10 ml per plant) application was (7.91%). Further, positive impact on the plant biomarkers was demonstrated by all selected Trichoderma isolates in greenhouse. Under natural infection in season I, the disease severity (%) after T. longibrachiatum, T. atroviride and T. harzianum treatments was 11.5, 13.26 and 16.81%, respectively, followed by control (32.12%), whereas 7.18% disease severity was recorded after fungicide application.

Conclusions
The results revealed that native Trichoderma of this region had potential to mitigate the early blight disease intensity in field.
Is hypoalbuminemia a risk factor for high-dose methotrexate toxicity in children with acute lymphoblastic leukemia?
Authors: Barakat Shaimaa , Assem Hala , Salama Mostafa , Mikhael Neveen , El Chazli Yasmine 
Published: April 2022

AbstractBackgroundRepeated high-dose methotrexate (HDMTX) is a critical component of contemporary childhood acute lymphoblastic leukemia (ALL) treatment regimens. Serum albumin is considered a carrier of methotrexate (MTX) in the blood. Hypoalbuminemia is not a rare finding in children with leukemia. This study aimed to investigate the relationship between pre-infusion serum albumin and possible HDMTX toxicities.MethodsThirty Egyptian children with ALL were consecutively enrolled in the study between May 2018 and July 2020. They were prospectively followed up while receiving HDMTX during the consolidation phase of the TOTAL study XV protocol. HDMTX was administered intravenously as a 24-h infusion every 2 weeks. Doses of 2.5 g/m2were used for low-risk patients and 5 g/m2for standard/high-risk patients. The Common Terminology Criteria for Adverse Events (V.4.03) was used to report the observed toxicities after HDMTX cycles. Plasma MTX levels were estimated at 24 h (MTX24) from the beginning of HDMTX infusion in the first consolidation cycle. Serum albumin level was determined before HDMTX administration, and pre-infusion hypoalbuminemia was defined when serum albumin was <3.5 g/dL.ResultsThe patients’ age ranged from 2.3 to 13.3 years at diagnosis, and most of them had B cell ALL (86.7%). Overall, 120 HDMTX cycles were analyzed, equally distributed between low and standard/high risk. Grade 3–4 anemia, grades 3–4 thrombocytopenia, febrile neutropenia, and oral mucositis were significantly more frequent in HDMTX cycles with pre-infusion hypoalbuminemia than those with normal pre-infusion albumin (p=0.003,p=0.007,p=0.006, andp=0.001, respectively). In addition, pre-infusion hypoalbuminemia was significantly associated with additional hospitalization due to HDMTX toxicity (p=0.031). Most HDMTX toxicities were comparable irrespective of the MTX dose. Oral mucositis was more frequently encountered in the 2.5 g/m2than the 5 g/m2HDMTX cycles (46.7 vs. 26.7%,p=0.023). A significantly longer hospitalization (due to HDMTX toxicity) was observed in the 5 g/m2HDMTX cycles (median= 7 days vs. 4 days,p=0.012).ConclusionsSerum albumin levels should be checked before starting HDMTX cycles, especially in resource-limited settings where malnutrition is common, and serum MTX monitoring may not be available. Optimizing serum albumin levels before HDMTX may help decrease the possibility of HDMTX toxicities.
Maternal supplementation of α-lipoic acid attenuates prenatal cytarabine exposure-induced oxidative stress, steroidogenesis suppression and testicular damage in F1 male rat fetus
Authors: Namoju Ramanachary , Chilaka Naga Kavitha 
Published: April 2022

Abstract
Background
Cytarabine (Ara-C) is an anticancer drug, which is considered as the mainstay in the treatment of hematological malignancies, known to cause various teratogenic effects. Alpha-lipoic acid (ALA) is a natural antioxidant and its supplementation proved to improve pregnancy outcomes in several pathological conditions. We aimed at exploring the benefits of maternal supplementation of ALA against in-utero Ara-C exposure-induced testicular toxicity in rat fetuses.

Methods
Pregnant rats (dams) received normal saline (control group), ALA 200 mg/kg (ALA group), Ara-C 12.5 mg/kg (Ara-C 12.5 group), Ara-C 25 mg/kg (Ara-C 25 group), and Ara-C 25 mg/kg + ALA 200 mg/kg (protection group) from gestational day (GD)8 to GD21. Ara-C and ALA were administered via the intraperitoneal and oral routes, respectively. The day of parturition was considered as postnatal day (PND)1. On PND1, all the live male pups were collected. The maternal parameters evaluated include (a) food intake, (b) bodyweight, and (c) oxidative stress (OS) markers. The fetal parameters evaluated include (a) bodyweight, (b) anogenital distances (AGD), (c) testicular weight (d) testicular testosterone levels (e) testicular histopathology, and (f) morphometrical parameters.

Results
A significant and dose-dependent decrease in maternal food intake, weight gain, and an increase in oxidative stress (OS) were observed in the pregnant rats of the Ara-C groups as compared to pregnant rats of the control group. Further, a significant and dose-dependent (a) reduction in bodyweight, AGD, testicular weight, and testosterone levels, (b) increase in OS, and (c) structural and morphometrical anomalies in fetal testes were observed in fetuses of Ara-C groups as compared to fetuses of the control rats. These deleterious effects observed in the Ara-C groups were found to be diminished in the pregnant rats and fetuses of the Protection group as compared to the pregnant rats and fetuses of the Ara-C 25 group.

Conclusions
From the results of this study, we conclude that the maternal supplementation of ALA may ameliorate the Ara-C exposure-induced impairment in prenatal development and function of the testes in the rat fetuses. However, future experimental and clinical studies are warranted to explore the possible mechanisms involved in the protection offered by maternal supplementation of ALA against Ara-C induced testicular toxicity.

Graphical Abstract