bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electro-acupuncture for protracted amphetamine abstinence syndrome: study protocol for a pragmatic randomized controlled trial
Authors: Ren Huan , Zeng Yiwei , Zhang Min , Zhang Su , Chen Zhihan , Wu Binbin , Liu Jun , Ren Yulan 
Published: March 2022

Abstract
Background
Protracted amphetamine abstinence syndrome is one of the primary causes of relapse for amphetamine-type drug abusers during withdrawal. However, the importance of the management of protracted amphetamine abstinence syndrome is underestimated. Electro-acupuncture may be a safe and effective alternative therapy for protracted amphetamine abstinence syndrome, but the evidence is limited.

Methods
The study is a prospective, two-center, randomized, waitlist controlled, open-label pragmatic trial. A total of 300 patients with protracted amphetamine abstinence syndrome will be recruited. All participants will be randomly assigned to an electro-acupuncture group or a waitlist group in a 1:1 ratio. Participants in the electro-acupuncture group will receive the electrical-acupuncture treatment. Waitlist group participants will not receive electro-acupuncture treatment but will be assessed at each visit. Treatments will be administered twice a week for a total of 4 consecutive weeks. The primary outcome in this study is the change in the ACSA between baseline (week 0) and the completion of treatment (week 4), and the secondary outcomes are changes in the Hamilton Depression Scale (HAMD), the visual analog scale (VAS), the Hamilton Anxiety Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Montreal Cognitive Assessment (MoCA), and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36).

Discussion
This study will assess the effectiveness of acupuncture in PAAS in real-world settings to provide support for clinical decisions and a basis for subsequent trials comparing acupuncture with other positive regimens.

Trial registration
ClinicalTrials.gov ChiCTR2000040619. Registered on 3 December 2020
Effectiveness of herb-partitioned moxibustion on the navel for pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer: a study protocol for a randomized controlled trial
Authors: Xia Qingchang , Gao Shuzhong , Song Jingyan , Du Dongqing , Li Chunjing , Zhou Yue , Zhang Xiaobin , Dong Zhibin , Ma Yuning , Ma Yuxia 
Published: March 2022

Abstract
Background
Recurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER), and immunity. The incidence of RIF is usually between 5 and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aims to evaluate the effectiveness and safeness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF.

Methods
This study conducts a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. No intervention will be used in the control group for 3 menstrual cycles. In the fourth menstrual cycle, all patients will undergo artificial cycle to prepare the endometrium for FET. The pregnancy outcomes will be recorded after a 3-month follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate, and clinical pregnancy rate.

Discussion
If the results show that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended in clinical practice.

Trial registration
Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100043954. Registered on 8 July 2021.
Updated occurrence and bionomics of potential malaria vectors in Europe: a systematic review (2000–2021)
Authors: Bertola Michela , Mazzucato Matteo , Pombi Marco , Montarsi Fabrizio 
Published: March 2022

AbstractDespite the eradication of malaria across most European countries in the 1960s and 1970s, the anopheline vectors are still present. Most of the malaria cases that have been reported in Europe up to the present time have been infections acquired in endemic areas by travelers. However, the possibility of acquiring malaria by locally infected mosquitoes has been poorly investigated in Europe, despite autochthonous malaria cases having been occasionally reported in several European countries. Here we present an update on the occurrence of potential malaria vector species in Europe. Adopting a systematic review approach, we selected 288 papers published between 2000 and 2021 for inclusion in the review based on retrieval of accurate information on the followingAnophelesspecies:An. atroparvus,An. hyrcanussensu lato (s.l.),An. labranchiae,An. maculipennissensu stricto (s.s.),An. messeae/daciae,An. sacharovi,An. superpictusandAn. plumbeus. The distribution of these potential vector species across Europe is critically reviewed in relation to areas of major presence and principal bionomic features, including vector competence toPlasmodium. Additional information, such as geographical details, sampling approaches and species identification methods, are also reported. We compare the information on each species extracted from the most recent studies to comparable information reported from studies published in the early 2000s, with particular reference to the role of each species in malaria transmission before eradication. The picture that emerges from this review is that potential vector species are still widespread in Europe, with the largest diversity in the Mediterranean area, Italy in particular. Despite information on their vectorial capacity being fragmentary, the information retrieved suggests a re-definition of the relative importance of potential vector species, indicatingAn. hyrcanuss.l.,An. labranchiae,An. plumbeusandAn. sacharovias potential vectors of higher importance, whileAn. messeae/daciaeandAn. maculipenniss.s. can be considered to be moderately important species. In contrast,An. atroparvusandAn. superpictusshould be considered as vectors of lower importance, particularly in relation to their low anthropophily. The presence of gaps in current knowledge of vectorial systems in Europe becomes evident in this review, not only in terms of vector competence but also in the definition of sampling approaches, highlighting the need for further research to adopt the appropriate surveillance system for each species.Graphical Abstract
Susceptibility of female rats to cardiac arrhythmias following refeeding after severe food restriction
Authors: De Souza Aline M. A. , Almeida Jonathas F. Q. , Shults Nataliia , Ji Hong , Li James , Sandberg Kathryn 
Published: March 2022

Abstract
Background
Many studies have shown malnutrition and inadequate caloric consumption have adverse acute effects on cardiovascular structure and function.

Methods
To determine the adverse long term cardiovascular effects, we studied cardiac morphology and function in female (F) and male (M) severe food restricted rats 3 months after refeeding (sFR-Refed).

Results
Two weeks of a normal chow diet in which calories were reduced by 60% decreased body weight (BW) by approximately 15% in both sexes. Within 2 weeks of refeeding, no differences in BW were detected between CT and sFR-Refed groups. However, male rats gained almost 3 times more BW than the females over the 3-month refeeding period. Sex differences were also observed in cardiac pathology. Hearts from F-sFR-Refed rats exhibited more atrophy and less hypertrophy, while M-sFR-Refed rats predominantly exhibited hypertrophic remodeling. While there were no differences in the frequency of ventricular arrhythmias induced by ischemia/reperfusion (I/R) in the isolated heart between M-CT and M-sFR-Refed rats, I/R induced twice as many arrhythmias in the F-sFR-Refed rats compared to F-CT.

Conclusions
These findings indicate the female heart is more susceptible to the long term adverse cardiovascular effects of sFR months after refeeding. Thus, this study provides a rationale for studying sex differences in cardiovascular risk in individuals who experience sFR for voluntary (e.g., very low-calorie dieting) or involuntary (e.g., poverty) reasons earlier in life.
Decomposing compounds enables reconstruction of interaction fingerprints for structure-based drug screening
Authors: Adasme Melissa F. , Bolz Sarah Naomi , Al-Fatlawi Ali , Schroeder Michael 
Published: March 2022

Abstract
Background
Structure-based drug repositioning has emerged as a promising alternative to conventional drug development. Regardless of the many success stories reported over the past years and the novel breakthroughs on the AI-based system AlphaFold for structure prediction, the availability of structural data for protein–drug complexes remains very limited. Whereas the chemical libraries contain millions of drug compounds, the vast majority of them do not have structures to crystallized targets,and it is, therefore, impossible to characterize their binding to targets from a structural view. However, the concept of building blocks offers a novel perspective on the structural problem. A drug compound is considered a complex of small chemical blocks or fragments, which confer the relevant properties to the drug and have a high proportion of functional groups involved in protein binding. Based on this, we propose a novel approach to expand the scope of structure-based repositioning approaches by transferring the structural knowledge from a fragment to a compound level.

Results
We fragmented over 100,000 compounds in the Protein Data Bank (PDB) and characterized the structural binding mode of 153,000 fragments to their crystallized targets. Using the fragment’s data, we were able to artificially reconstruct the binding mode of over 7,800 complexes between ChEMBL compounds and their known targets, for which no structural data is available. We proved that the conserved binding tendency of fragments, when binding to the same targets, highly influences the drug’s binding specificity and carries the key information to reconstruct full drugs binding mode. Furthermore, our approach was able to reconstruct multiple compound-target pairs at optimal thresholds and high similarity to the actual binding mode.

Conclusions
Such reconstructions are of great value and benefit structure-based drug repositioning since they automatically enlarge the technique’s scope and allow exploring the so far ‘unexplored compounds’ from a structural perspective. In general, the transfer of structural information is a promising technique that could be applied to any chemical library, to any compound that has no crystal structure available in PDB, and even to transfer any other feature that may be relevant for the drug discovery process and that due to data limitations is not yet fully available. In that sense, the results of this work document the full potential of structure-based screening even beyond PDB.

Graphical Abstract
A multitask GNN-based interpretable model for discovery of selective JAK inhibitors
Authors: Wang Yimeng , Gu Yaxin , Lou Chaofeng , Gong Yuning , Wu Zengrui , Li Weihua , Tang Yun , Liu Guixia 
Published: March 2022

AbstractThe Janus kinase (JAK) family plays a pivotal role in most cytokine-mediated inflammatory and autoimmune responses via JAK/STAT signaling, and administration of JAK inhibitors is a promising therapeutic strategy for several diseases including COVID-19. However, to screen and design selective JAK inhibitors is a daunting task due to the extremely high homology among four JAK isoforms. In this study, we aimed to simultaneously predict pIC50 values of compounds for all JAK subtypes by constructing an interpretable GNN multitask regression model. The final model performance was positive, with R2 values of 0.96, 0.79 and 0.78 on the training, validation and test sets, respectively. Meanwhile, we calculated and visualized atom weights, followed by the rank sum tests and local mean comparisons to obtain key atoms and substructures that could be fine-tuned to design selective JAK inhibitors. Several successful case studies have demonstrated that our approach is feasible and our model could learn the interactions between proteins and small molecules well, which could provide practitioners with a novel way to discover and design JAK inhibitors with selectivity.
Graphical Abstract
SSEP N20 and P25 amplitudes predict poor and good neurologic outcomes after cardiac arrest
Authors: Benghanem Sarah , Nguyen Lee S. , Gavaret Martine , Mira Jean-Paul , Pène Frédéric , Charpentier Julien , Marchi Angela , Cariou Alain 
Published: March 2022

Abstract
Background
To assess in comatose patients after cardiac arrest (CA) if amplitudes of two somatosensory evoked potentials (SSEP) responses, namely, N20-baseline (N20-b) and N20–P25, are predictive of neurological outcome.

Methods
Monocentric prospective study in a tertiary cardiac center between Nov 2019 and July-2021. All patients comatose at 72 h after CA with at least one SSEP recorded were included. The N20-b and N20–P25 amplitudes were automatically measured in microvolts (µV), along with other recommended prognostic markers (status myoclonus, neuron-specific enolase levels at 2 and 3 days, and EEG pattern). We assessed the predictive value of SSEP for neurologic outcome using the best Cerebral Performance Categories (CPC1 or 2 as good outcome) at 3 months (main endpoint) and 6 months (secondary endpoint). Specificity and sensitivity of different thresholds of SSEP amplitudes, alone or in combination with other prognostic markers, were calculated.

Results
Among 82 patients, a poor outcome (CPC 3–5) was observed in 78% of patients at 3 months. The median time to SSEP recording was 3(2–4) days after CA, with a pattern “bilaterally absent” in 19 patients, “unilaterally present” in 4, and “bilaterally present” in 59 patients. The median N20-b amplitudes were different between patients with poor and good outcomes, i.e., 0.93 [0–2.05]µV vs. 1.56 [1.24–2.75]µV, respectively (p < 0.0001), as the median N20–P25 amplitudes (0.57 [0–1.43]µV in poor outcome vs. 2.64 [1.39–3.80]µV in good outcome patients p < 0.0001). An N20-b > 2 µV predicted good outcome with a specificity of 73% and a moderate sensitivity of 39%, although an N20–P25 > 3.2 µV was 93% specific and only 30% sensitive. A low voltage N20-b < 0.88 µV and N20–P25 < 1 µV predicted poor outcome with a high specificity (sp = 94% and 93%, respectively) and a moderate sensitivity (se = 50% and 66%). Association of “bilaterally absent or low voltage SSEP” patterns increased the sensitivity significantly as compared to “bilaterally absent” SSEP alone (se = 58 vs. 30%, p = 0.002) for prediction of poor outcome.

Conclusion
In comatose patient after CA, both N20-b and N20–P25 amplitudes could predict both good and poor outcomes with high specificity but low to moderate sensitivity. Our results suggest that caution is needed regarding SSEP amplitudes in clinical routine, and that these indicators should be used in a multimodal approach for prognostication after cardiac arrest.
Role of hard X-ray emission in ionospheric D-layer disturbances during solar flares
Authors: Briand Carine , Clilverd Mark , Inturi Srivani , Cecconi Baptiste 
Published: March 2022

AbstractAny disturbance of the ionosphere may affect operational activities based on HF communication. The electron density is a critical parameter that controls levels of HF-signal absorption. A significant part of the HF absorption takes place in the D-layer. The increase of X radiations during solar flares generates noticeable perturbations of the electron density of the D-layer. However, the ionosphere reacts with some delay to the solar forcing. Several studies have addressed this question of ionospheric sluggishness from the time delay between VLF narrow-band transmissions and soft X-ray emissions during solar flares. Our study initially considers the interpretation of the VLF amplitude time profile. In particular, we show that the maximum of X-ray emission can be associated with a reversal in the VLF amplitude variation with time, i.e. exhibiting a peak or a trough. Then, building on this insight, we perform estimates of the time delay between VLF and soft X-rays during 67 events between 2017 and 2021, thus including the major flares of 2017. We show that the time delay can become negative for flares above X2, proving that soft X-rays are not the initial source of ionization in the case of major flares. From a careful analysis of RHESSI data for some events of September 2017, we demonstrate that radiation above 40 keV (i.e. hard X-rays) is an important forcing source of the ionosphere. This is of crucial interest in the frame of space weather forecasting since the hard X-rays are produced several minutes before the peak of soft X-rays.
Graphical Abstract
Decreased myostatin in response to a controlled DASH diet is associated with improved body composition and cardiometabolic biomarkers in older adults: results from a controlled-feeding diet intervention study
Authors: Perry Cydne A. , Van Guilder Gary P. , Butterick Tammy A. 
Published: March 2022

Abstract
Background
Elevated concentrations of myostatin inhibit muscle growth, function and strength. Myostatin is a mediator of sarcopenia and is associated with insulin resistance. For this study we tested the response of a calorie-restricted Dietary Approaches to Stop Hypertension (DASH) diet on changes in myostatin, follistatin, and mystatin:follistatin ratio levels after 12 weeks in comparison to basline in adults aged 65 years and older. Furthermore we evaluated correlations between changes in myostatin, body composition and cardiometabolic biomarkers in this cohort of older adults.

Methods
This was a controlled-feeding diet intervention study in which females (n = 17) and males (n = 11) aged 65 years and older consumed either 85 g (n = 15) or 170 g (n = 13) of fresh lean beef within a standardized DASH diet for 12-weeks. Myostatin and follistatin concentrations were measured from fasted blood samples collected at 5 timepoints throughout the 12-week feeding intervention period. Correlations were assessed between changes in myostatin and follistatin levels and measures of body composition and cardiometabolic biomarkers.

Results
There were no differences (p > 0.05) in circulating myostatin or follistatin levels between the beef intake groups. However, with beef groups combined myostatin decreased by 17.6% (p = 0.006) and the myostatin-to-follistatin ratio decreased by 16.5% (p < 0.001) in response to the study diet. Decreased myostatin was positively correlated with reductions in waist circumference (R2 = 0.163; p = 0.033) and fat mass (R2 = 0.233; p = 0.009). There was an inverse relationship between decreased myostatin and increased strength-to-weight ratio (R2 = 0.162; p = 0.034). The change in myostatin-to-follistatin ratio was associated with the change in skeletal muscle mass-to-fat mass ratio (R2 = 0.176; p = 0.026). Decreased myostatin was positively correlated with reductions in total cholesterol (R2 = 0.193; p = 0.012), LDL-C (R2 = 0.163; p = 0.031), insulin (R2 = 0.234; p = 0.009), and HOMA-IR (R2 = 0.248; P = 0.007). There was no change (p > 0.05) in circulating follistatin concentrations in response to the diet intervention.

Conclusions
The outcomes from this study suggest that a calorie-restricted DASH diet has the potential to reduce myostatin concentrations in older adults. Furthermore these outcomes support interrelationships between myostatin, body composition and cardiometabolic health in adults aged 65 years and older.

Trial registration
ClinicalTrials.gov; Identifier: NCT04127240; Registration Date: 15/10/ 2019.
Evaluation of the quality of online patient information at the intersection of complementary and alternative medicine and hypertension
Authors: Ng Jeremy Y. , Jomy Jane , Vacca Alexandra 
Published: March 2022

Abstract
Background
Hypertension impacts 1.1 billion people globally; many patients seek complementary and alternative medicine (CAM), as a result of adverse side effects from antihypertensive medications or because they believe natural options are safer. The internet is increasingly playing a role in patient health information-seeking behavior, however, the variability of information quality across websites is unclear. Thus, the purpose of this study was to assess the quality of websites providing consumer health information at the intersection of hypertension and CAM.

Methods
Four unique terms were searched on Google, across Australia, Canada, the US, and the UK. The first 20 webpages resulting from each search were screened for eligibility, and were included if they contained consumer health information relating to CAM therapies for the treatment/management of hypertension. To assess the quality of health information on eligible websites, we used the DISCERN instrument, a standardized quality index of consumer health information.

Results
Of 90 unique webpages, 40 websites were deemed eligible and quality assessed. The 40 eligible websites were classified into seven categories: professional (n = 15), news (n = 11), non-profit (n = 5), health portal (n = 3), commercial (n = 2), government (n = 1), and other (n = 3). The mean summed DISCERN score was 52.34 (standard deviation [SD] = 10.69) out of 75 and the mean overall score was 3.49 (SD = 0.08) out of 5. A total of 10 websites had a total DISCERN score of 60.00 and above with an average rating of 4.33. Among these, Medicine Net (69.00) and WebMD (69.00) were determined to have the highest quality information. Websites generally scored well with respect to providing their aims, identifying treatment benefits and options, and discussing shared-decision making; websites generally lacked references and provided inadequate information surrounding treatment risks and impact on quality of life.

Conclusions
While some websites provided high-quality consumer health information, many others provided information of suboptimal quality. A need exists to better educate patients about identifying misinformation online. Healthcare providers should also inquire about their patients’ health information-seeking behavior, and provide them with the guidance necessary to identify high-quality resources which they can use to inform shared-decision making.