bluuebunny/crossref_metadata_2025 huggingface dataset:
The magnetic fields and stellar winds of the mature late F-stars: β Virginis and θ Draconis
Authors: Seach J M , Marsden S C , Carter B D , Evensberget D , Folsom C P , Neiner C , Mengel M W
Published: November 2021

Mapping the large-scale magnetic field in late F-type stars is important for understanding the nature of the stellar dynamo and the dynamics of thin outer convection zones. We use Zeeman Doppler Imaging to produce multi-epoch maps of the surface magnetic field for two mature late F-type stars: β Virginis (F9V) and θ Draconis (F8IV). We also provide a magnetohydrodynamic model for the stellar winds from the corona to the inner astrosphere, which exists in an environment at the hot end of habitability for exoplanets. Our results show that either simple or complex dynamo magnetic fields are present in mature late F-type stars, with shallow outer convection zones. The results of stellar wind modelling show the average space weather for β Vir at a distance of 1 au falls within the range of space weather conditions observed at Earth, while θ Dra produces a wind pressure an order of magnitude stronger than the Sun’s wind pressure.
Spectral and temporal properties of ultra-luminous X-ray source NGC 55 ULX1
Authors: Jithesh V
Published: November 2021

We investigate the spectral and temporal properties of ultra-luminous X-ray source (ULX) NGC 55 ULX1 using Swift, XMM-Newton and NuSTAR observations conducted during 2013–2021. In these observations, the source flux varies by a factor of ∼5–6, and we identify the source mainly in the soft ultraluminous (SUL) state of ULXs. We fit the X-ray spectra with a two thermal component model consisting of a blackbody (for the soft component) and a disc (for the hard component), and the soft component dominates in these observations. The soft component in the SUL state shows properties similar to that of ultraluminous supersoft sources, for example, an anticorrelation between the characteristic radius and temperature of the blackbody component. In addition, we observe a positive correlation between the blackbody and inner disc temperatures when the X-ray spectra are fitted with the two-thermal component model. The source exhibits marginal evidence of X-ray flux dips in the Swift and XMM-Newton observations at different intensity levels. We explain the observed spectral and temporal properties of the source by invoking the supercritical radiatively driven outflow mechanism.
Uncertainty-aware and interpretable evaluation of Cas9–gRNA and Cas12a–gRNA specificity for fully matched and partially mismatched targets with Deep Kernel Learning
Authors: Kirillov Bogdan , Savitskaya Ekaterina , Panov Maxim , Ogurtsov Aleksey Y , Shabalina Svetlana A , Koonin Eugene V , Severinov Konstantin V
Published: November 2021

The choice of guide RNA (gRNA) for CRISPR-based gene targeting is an essential step in gene editing applications, but the prediction of gRNA specificity remains challenging. Lack of transparency and focus on point estimates of efficiency disregarding the information on possible error sources in the model limit the power of existing Deep Learning-based methods. To overcome these problems, we present a new approach, a hybrid of Capsule Networks and Gaussian Processes. Our method predicts the cleavage efficiency of a gRNA with a corresponding confidence interval, which allows the user to incorporate information regarding possible model errors into the experimental design. We provide the first utilization of uncertainty estimation in computational gRNA design, which is a critical step toward accurate decision-making for future CRISPR applications. The proposed solution demonstrates acceptable confidence intervals for most test sets and shows regression quality similar to existing models. We introduce a set of criteria for gRNA selection based on off-target cleavage efficiency and its variance and present a collection of pre-computed gRNAs for human chromosome 22. Using Neural Network Interpretation methods, we show that our model rediscovers an established biological factor underlying cleavage efficiency, the importance of the seed region in gRNA.
An archaeal histone-like protein regulates gene expression in response to salt stress
Authors: Sakrikar Saaz , Schmid Amy K
Published: November 2021

Histones, ubiquitous in eukaryotes as DNA-packing proteins, find their evolutionary origins in archaea. Unlike the characterized histone proteins of a number of methanogenic and themophilic archaea, previous research indicated that HpyA, the sole histone encoded in the model halophile Halobacterium salinarum, is not involved in DNA packaging. Instead, it was found to have widespread but subtle effects on gene expression and to maintain wild type cell morphology. However, the precise function of halophilic histone-like proteins remain unclear. Here we use quantitative phenotyping, genetics, and functional genomics to investigate HpyA function. These experiments revealed that HpyA is important for growth and rod-shaped morphology in reduced salinity. HpyA preferentially binds DNA at discrete genomic sites under low salt to regulate expression of ion uptake, particularly iron. HpyA also globally but indirectly activates other ion uptake and nucleotide biosynthesis pathways in a salt-dependent manner. Taken together, these results demonstrate an alternative function for an archaeal histone-like protein as a transcriptional regulator, with its function tuned to the physiological stressors of the hypersaline environment.
Dynamic modulation of enhancer responsiveness by core promoter elements in living Drosophila embryos
Authors: Yokoshi Moe , Kawasaki Koji , Cambón Manuel , Fukaya Takashi
Published: November 2021

Regulatory interactions between enhancers and core promoters are fundamental for the temporal and spatial specificity of gene expression in development. The central role of core promoters is to initiate productive transcription in response to enhancer's activation cues. However, it has not been systematically assessed how individual core promoter elements affect the induction of transcriptional bursting by enhancers. Here, we provide evidence that each core promoter element differentially modulates functional parameters of transcriptional bursting in developing Drosophila embryos. Quantitative live imaging analysis revealed that the timing and the continuity of burst induction are common regulatory steps on which core promoter elements impact. We further show that the upstream TATA also affects the burst amplitude. On the other hand, Inr, MTE and DPE mainly contribute to the regulation of the burst frequency. Genome editing analysis of the pair-rule gene fushi tarazu revealed that the endogenous TATA and DPE are both essential for its correct expression and function during the establishment of body segments in early embryos. We suggest that core promoter elements serve as a key regulatory module in converting enhancer activity into transcription dynamics during animal development.
Chromatin-contact atlas reveals disorder-mediated protein interactions and moonlighting chromatin-associated RBPs
Authors: Rafiee Mahmoud-Reza , Zagalak Julian A , Sidorov Sviatoslav , Steinhauser Sebastian , Davey Karen , Ule Jernej , Luscombe Nicholas M
Published: November 2021

RNA-binding proteins (RBPs) play diverse roles in regulating co-transcriptional RNA-processing and chromatin functions, but our knowledge of the repertoire of chromatin-associated RBPs (caRBPs) and their interactions with chromatin remains limited. Here, we developed SPACE (Silica Particle Assisted Chromatin Enrichment) to isolate global and regional chromatin components with high specificity and sensitivity, and SPACEmap to identify the chromatin-contact regions in proteins. Applied to mouse embryonic stem cells, SPACE identified 1459 chromatin-associated proteins, ∼48% of which are annotated as RBPs, indicating their dual roles in chromatin and RNA-binding. Additionally, SPACEmap stringently verified chromatin-binding of 403 RBPs and identified their chromatin-contact regions. Notably, SPACEmap showed that about 40% of the caRBPs bind chromatin by intrinsically disordered regions (IDRs). Studying SPACE and total proteome dynamics from mES cells grown in 2iL and serum medium indicates significant correlation (R = 0.62). One of the most dynamic caRBPs is Dazl, which we find co-localized with PRC2 at transcription start sites of genes that are distinct from Dazl mRNA binding. Dazl and other PRC2-colocalised caRBPs are rich in intrinsically disordered regions (IDRs), which could contribute to the formation and regulation of phase-separated PRC condensates. Together, our approach provides an unprecedented insight into IDR-mediated interactions and caRBPs with moonlighting functions in native chromatin.
UN Sustainable Development Goals and the “Refugee Gap”: Leaving Refugees Behind?
Authors: Denaro Chiara , Giuffré Mariagiulia
Published: November 2021

The Global Indicator Framework for the Sustainable Development Goals (SDGs) identifies seventeen goals with related targets and indicators of the 2030 Agenda for Sustainable Development, and only one target includes an explicit reference to migration processes and policies. Under Goal 10 “Reduce inequality within and among countries,” target 10.7 concerns the facilitation of “orderly, safe, regular and responsible migration, and mobility of people, which includes the implementation of planned and well-managed migration policies” that should be measured through four related indicators, three of which are potentially relevant to refugees. After exploring what the International Rescue Committee defines as “refugee gap” concerning SDGs (2019) in their report “Missing Persons: Refugees Left Out and Left Behind in SDGs,” this article reconfigures this gap as a multidimensional concept, and seeks to provide insights on which further steps could be undertaken to bridge it. The main analytical threads identified in this process include: 1) the partial availability of data concerning refugees” progress towards SDGs due to current data disaggregation policies and practices; 2) the limited presence of refugees in voluntary reporting activities by States; and 3) the conceptual framework behind target 10.7, as well as the methodology used to measure progress of three (out of four) indicators toward this target. The focus on target 10.7 and related indicators is aimed at checking their ability to provide information on how refugees’ access to fundamental rights and well-being are taken into account in the assessment of so-called “well managed migration policies.” From a methodological point of view, our analysis has also been supported by semi-structured interviews with the main experts on the issue, having key roles both in the conceptualization of the SDG refugee gap and in the definition and proposal of three selected indicators. To conclude, this article will ask whether and to what extent the refugee gap is still present despite the inclusion of a new refugee dedicated indicator in 2020 and despite the UNHCR’s advocacy efforts to include the forcibly displaced dimension in disaggregation policies. Moreover, it will investigate how such a gap can potentially be closed and whether the definition of “well-managed migration policies” is sufficiently comprehensive, is able to involve refugees in the assessment of progress towards SDGs and is consistent with the SDGs-linked principle of “leaving no one behind.”
Not All Good Is Care, Not All Evil Is Uncaring—A Political Comment on The Care Manifesto
Authors: Esquivel Valeria
Published: November 2021

This short comment focuses on The Care Manifesto's vision “to think of care as the organizing principle of each and every scale of life”. It challenges the construction of care as a universal, all-ecompasing concept, on conceptual and political grounds: naming everything good care and everything evil uncaring leaves us with too simplistic a picture of the problems at hand; and makes the necessary political alliances to move the care agenda forward harder to forge. This is all the more so when The Care Manifesto also evidences a strong localism, as examples come mainly from the United Kingdom and the United States. In the urgent need to create a collective care narrative, and broadening the care agenda, The Care Manifesto is one important contribution, but many more voices, situations, locations and allies are necessary.
Comparison of Shock Index With the Assessment of Blood Consumption Score for Association With Massive Transfusion During Hemorrhage Control for Trauma
Authors: Day Darcy L. , Ng Karen , Huang Jonathan B. , Severino Richard , Hayashi Michael S.
Published: November 2021

Background:

Hemorrhage is a leading cause of early mortality following trauma. A massive transfusion protocol (MTP) to guide resuscitation while bleeding is definitively controlled may improve outcomes. Prompts to initiate massive transfusion (MT) include shock index (SI) and the Assessment of Blood Consumption (ABC) score.

Objective:

To compare SI with the ABC score for association with transfusion requirement, need for emergency hemorrhage interventions, and early mortality.

Methods:

A retrospective cohort analysis of trauma MTP activations at our Level I trauma center was conducted from January 1, 2012, to December 31, 2016. The study data were obtained from the Trauma Registry and the blood bank. An SI cutoff of 1.0 was chosen for comparison with the positive ABC score.

Results:

The study cohort included 146 patients. Shock index ≥ 1 had significant association with MT requirement (p = .002) whereas a positive ABC score did not (p = .65). More patients with SI ≥ 1 required bleeding control interventions (67% surgery, 47% interventional radiology) than patients having a positive ABC score (49% surgery, 29% interventional radiology). For geriatric patients who received MT, 65% had SI ≥ 1 but only 30% had a positive ABC score. Three-hour mortality following emergency department arrival was similar (60% SI ≥ 1, 62% positive ABC score).

Conclusion:

Shock index ≥ 1 outperformed a positive ABC score for association with MT requirement. Shock index is a simple tool registered nurses can independently utilize to anticipate MT.
Effects of Acupuncture and Acupressure on Burnout in Health Care Workers: A Randomized Trial
Authors: Afrasiabi Julia , McCarty Ruth , Hayakawa Jennifer , Barrows Jennifer , Lee Kent , Plouffe Nicole , Schomberg John
Published: November 2021

Background:

Health care workers face occupational stressors that may lead to burnout and secondary traumatic stress. Strategies to mitigate the negative psychological impact on frontline workers are urgently needed.

Objective:

The purpose of this study was to evaluate the effect of auricular acupuncture or acupressure, as compared with ear massage, on anxiety, burnout, and caring capacity in health care workers. Results were stratified on the basis of subject's level of belief in traditional Chinese medicine.

Methods:

This prospective randomized trial with an open, parallel-group design was conducted at a 334-bed Level II pediatric trauma center. Participants were randomized to one of three groups: (1) auricular acupuncture, (2) auricular seed acupressure, or (3) auricular massage. Interventions were delivered over 3 weeks. Self-reported State-Trait Anxiety Inventory (STAI), Professional Quality of Life (ProQOL), and Caring Ability Inventory (CAI) scores were analyzed using a pre-/posttest design. Univariate analysis, Fisher's exact test, and analysis of variance (ANOVA) were performed to assess group differences.

Results:

A total of 117 (36%) of 325 eligible participants consented to participate in the study. Seed acupressure treatment (n = 14, 35.9%, one male, 13 females) was associated with a reduction in burnout (ANOVA, p = .04) and secondary traumatic stress (p = .03). This effect remained significant after adjusting for individual pretest scores (ANOVA, p = .05). The studied interventions did not have a significant effect on STAI, ProQOL, or CAI scores.

Conclusions:

Auricular acupressure is a safe, effective, and practical strategy to reduce burnout and secondary traumatic stress and may support health care workers' ability to develop caring relationships with patients and families.
Improving Blunt Chest Wall Injury Outcomes: Introducing the PIC Score
Authors: Terry Shawn M. , Shoff Kimberly A. , Sharrah Mark L.
Published: November 2021

Background:

To improve care for nonintubated blunt chest wall injury patients, our Level I trauma center developed a treatment protocol and a pulmonary evaluation tool named “PIC Protocol” and “PIC Score,” emphasizing continual assessment of pain, incentive spirometry, and cough ability.

Objective:

The primary objective was to reduce unplanned intensive care unit admissions for blunt chest wall injury patients using the PIC Protocol and the PIC Score. Additional outcomes included intensive care unit length of stay, ventilator days, length of hospital stay, inhospital mortality, and discharge destination.

Methods:

This was a retrospective cohort study comparing outcomes of rib fracture patients treated at our facility 2 years prior to (control group) and 2 years following PIC Protocol use (PIC group). The protocol included admission screening, a power plan order set, the PIC Score patient assessment tool, in-room communication board, and patient education brochure. Outcomes were compared using independent-samples t tests for continuous variables and Pearson's χ2 for categorical variables with α set to p < .05.

Results:

There were 1,036 patients in the study (control = 501; PIC = 535). Demographics and injury severity were similar between groups. Unanticipated escalations of care for acute pulmonary distress were reduced from 3% (15/501) in the control group to 0.37% (2/535) in the PIC group and were predicted by a preceding fall in the PIC Score of 3 points over the previous 8-hr shift, marking pulmonary decline by an acutely falling PIC Score.

Conclusions:

The PIC Protocol and the PIC Score are easy-to-use, cost-effective tools for guiding care of blunt chest wall injury patients.
Transimpedance Matrix Measurements Reliably Detect Electrode Tip Fold-over in Cochlear Implantation
Authors: Hans Stefan , Arweiler-Harbeck Diana , Kaster Friederike , Ludwig Johannes , Hagedorn Elfriede , Lang Stephan , Meyer Moritz , Holtmann Laura Christine
Published: November 2021

Objective:

During cochlear implantation, electrophysiological tests are performed to document safe technical functioning of implant and electrodes. In rare cases, the apical part of the electrode folds over during insertion. The data from transimpedance matrix (TIM) measurements enable the generation of a heat map or TIM profile measuring the spatial distribution of voltage. The aim of this study was to determine the accuracy of heat-map TIM profiles and compare them with spread of excitation (SOE) measurements and intraoperative imaging for prediction of electrode malposition.

Study Design:

Non-randomized study.

Setting:

Tertiary referral center.

Patients and Interventions:

One hundred patients who underwent cochlear implantation with completed TIM measurements, SOE data and perioperative imaging met the inclusion criteria and were enrolled.

Main Outcome Measure:

The electrophysiological data on the electrode array positioning was compared with temporal bone imaging.

Results:

In seven cases, TIM measurements showed irregular results. In two cases, irregular TIM profiles were registered, but SOE data and 3D x-ray of the temporal bone didn’t display deviated electrode positioning. A 3D x-ray of the skull displayed electrode tip fold-over in four cases and electrode buckling in one case. Sensitivity of TIM measurements and SOE data was 100%, specificity of TIM measurements was 97.89%, and specificity of SOE data was 98.93%.

Conclusion:

Out of 100 patients using TIM measurements for detection of electrode malpositioning, no false negative cases were detected. TIM measurements successfully detect electrode malposition in an intraoperative setting. Different heat map patterns may be observed depending on location and type of malposition.
Bottom-Up Signal Quality Impacts the Role of Top-Down Cognitive-Linguistic Processing During Speech Recognition by Adults with Cochlear Implants
Authors: Moberly Aaron C. , Lewis Jessica H. , Vasil Kara J. , Ray Christin , Tamati Terrin N.
Published: November 2021

Hypotheses:

Significant variability persists in speech recognition outcomes in adults with cochlear implants (CIs). Sensory (“bottom-up”) and cognitive-linguistic (“top-down”) processes help explain this variability. However, the interactions of these bottom-up and top-down factors remain unclear. One hypothesis was tested: top-down processes would contribute differentially to speech recognition, depending on the fidelity of bottom-up input.

Background:

Bottom-up spectro-temporal processing, assessed using a Spectral-Temporally Modulated Ripple Test (SMRT), is associated with CI speech recognition outcomes. Similarly, top-down cognitive-linguistic skills relate to outcomes, including working memory capacity, inhibition-concentration, speed of lexical access, and nonverbal reasoning.

Methods:

Fifty-one adult CI users were tested for word and sentence recognition, along with performance on the SMRT and a battery of cognitive-linguistic tests. The group was divided into “low-,” “intermediate-,” and “high-SMRT” groups, based on SMRT scores. Separate correlation analyses were performed for each subgroup between a composite score of cognitive-linguistic processing and speech recognition.

Results:

Associations of top-down composite scores with speech recognition were not significant for the low-SMRT group. In contrast, these associations were significant and of medium effect size (Spearman's rho = 0.44–0.46) for two sentence types for the intermediate-SMRT group. For the high-SMRT group, top-down scores were associated with both word and sentence recognition, with medium to large effect sizes (Spearman's rho = 0.45–0.58).

Conclusions:

Top-down processes contribute differentially to speech recognition in CI users based on the quality of bottom-up input. Findings have clinical implications for individualized treatment approaches relying on bottom-up device programming or top-down rehabilitation approaches.
Intertrochanteric valgus osteotomy for post-traumatic coxa vara after proximal femur fractures
Authors: Tian Shuwei , Liu Meiyu , Zhang Jing , Zhang Lefang , Peng Aqin
Published: November 2021

To investigate the clinical effects of a new intertrochanteric valgus osteotomy technique designed by the authors for treatment of post-traumatic coxa varus after proximal femur fractures. Retrospectively analyzed 11 patients who developed coxa vara after sustaining proximal femoral fractures were treated with intertrochanteric valgus osteotomy from December 2005 to December 2018 in our hospital. This study included 6 cases of intertrochanteric fracture deformity union, 3 cases of subtrochanteric fracture nonunion and 2 cases of femoral neck fracture nonunion. Measured the degree of coxa varus, the differences in the lower limb length and force line in all patients. Evaluated hip function with the Harris hip score. All injuries were treated with the authors’ intertrochanteric valgus osteotomy technique. The average follow-up period was 3 years and evaluated the clinical effects by radiological examination and the Harris hip score. The average neck–shaft angle increased 35.0° (99.1°–134.1°) and the average limb shortening lengthened 1.9 cm (2.9–1.0 cm) after surgery. The average operating time was 67.2 minutes and blood loss was 237.7 ml. The osteotomy position healed in all patients 3 months later. Union of the 2 old femoral neck fractures was achieved 4 and 6 months after surgery, respectively, and no femoral head necrosis occurred during follow-up. The Harris hip score increased an average of 49 points (44.1–93.1 points) at 1 year postoperatively. Our self-designed intertrochanteric valgus osteotomy technique showed a favorable clinical effect to treatment coxa vara and can be used in the clinical setting.
Molecular genetics of β-thalassemia
Authors: Jaing Tang-Her , Chang Tsung-Yen , Chen Shih-Hsiang , Lin Chen-Wei , Wen Yu-Chuan , Chiu Chia-Chi
Published: November 2021

β-thalassemia is a hereditary hematological disease caused by over 350 mutations in the β-globin gene (HBB). Identifying the genetic variants affecting fetal hemoglobin (HbF) production combined with the α-globin genotype provides some prediction of disease severity for β-thalassemia. However, the generation of an additive composite genetic risk score predicts prognosis, and guide management requires a larger panel of genetic modifiers yet to be discovered.

Presently, using data from prior clinical trials guides the design of further research and academic studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene therapy approaches.

Genetic studies have successfully characterized the causal variants and pathways involved in HbF regulation, providing novel therapeutic targets for HbF reactivation. In addition to these HBB mutation-independent strategies involving HbF synthesis de-repression, the expanding genome editing toolkit provides increased accuracy to HBB mutation-specific strategies encompassing adult hemoglobin restoration for personalized treatment of hemoglobinopathies. Allogeneic hematopoietic stem cell transplantation was, until very recently, the curative option available for patients with transfusion-dependent β-thalassemia. Gene therapy currently represents a novel therapeutic promise after many years of extensive preclinical research to optimize gene transfer protocols.

We summarize the current state of developments in the molecular genetics of β-thalassemia over the last decade, including the mechanisms associated with ineffective erythropoiesis, which have also provided valid therapeutic targets, some of which have been shown as a proof-of-concept.
Evaluation of the efficiency and safety of combined chemotherapy and molecular-targeted therapy in the treatment of advanced gastric cancer
Authors: He Zhan , Xu Jian-Guo
Published: November 2021

Background:

Gastric cancer is considered to be the sixth prevalent cancer and the third widespread trigger of cancer-associated deaths globally. One of the major method of treating this harmful condition is completely resecting the entire tumor. Standard treatment procedures, including radiotherapy, surgery, and chemotherapy are ineffective for patients with advanced gastric cancer (AGC), mainly because the predictions are deficient. Many studies have recently sought to examine the effect of combining chemotherapy and molecular-targeted therapy, supposing that such developments could become effective for treating AGC. Still, the advantages of combining chemotherapy plus molecular-targeted therapy to treat advanced gastric cancer appear to be unconvincing.

Methods and analysis:

We intend to perform an electronic search using information obtained from PubMed, EMBASE, Cochrane Library, ScienceDirect, Web of Science, China National Knowledge Infrastructure, and WanFang databases. Specifically, we will consider all randomized controlled trials published in English or Chinese, and focus only on those assessing the effectiveness and safety of a MIC of chemotherapy and molecular-targeted therapy to treat AGC. Furthermore, two independent authors will conduct data extraction as well as explore the risk of bias. Furthermore, we intend to use the odds ratio for dichotomous data, mean differences or standardized mean differences for continuous data, along with hazard ratio for time-to-event data, with 95% confidence intervals (CIs).

Ethics and dissemination:

Because of the nature of this study, we will not require ethical approval. Instead, we will report the review reported in a peer-reviewed journal.
Neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios may not be useful markers to assess disease activity in rheumatoid arthritis
Authors: Lijuan Wang , Yuting Zhou , Chaoyang Liang , Ju Yang
Published: November 2021

The associations among the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) and disease activity in rheumatoid arthritis remains unclear.

To evaluate these indicators as potential markers of disease activity in patients with rheumatoid arthritis (RA).

This cross-sectional study included 547 adult patients with RA. The patients were divided into two groups according to the disease activity score (DAS) system: remission and disease activity. Differences in the NLR, PLR and LMR of the two groups were assessed. Correlations were analyzed using Spearman analysis, and receiver operating characteristic (ROC) curves were used to identify the sensitivity, specificity, and optimal cutoff values to differentiate active RA patients from inactive RA patients.

There was a statistically significant difference in the NLR (4.2 ± 3.2 vs 3.4 ± 2.4, P = .034) and PLR (222.3 ± 136.4 vs 176.9 ± 89.8, P = .006) between the two groups, but not for the LMR (3.0 ± 1.8 vs 3.4 ± 2.4, P = .115). In addition, the DAS28 and traditional inflammatory markers, including ESR and CRP, were weakly positively correlated with the NLR and PLR. Based on the ROC curves, the NLR (sensitivity 31.8%, specificity 77.8%) and PLR (sensitivity 57.3%, specificity 63.9%) were less valuable than the ESR (sensitivity 67.2%, specificity 91.7%) and CRP (sensitivity 76.2%, specificity 91.7%) for differentiating inactive RA patients from active RA patients due to low sensitivity and specificity and combining NLR or PLR also cannot significantly improved the diagnostic value of ESR and CRP.

NLR, PLR and LMR may not be an useful independent diagnostic or complementary marker for disease activity in RA patients.
Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus
Authors: Higashikawa Toshihiro , Ito Tomohiko , Mizuno Takurou , Ishigami Keiichirou , Kuroki Kengo , Maekawa Naoto , Usuda Daisuke , Morita Takuro , Hamada Kazu , Takagi Susumu , Takeshima Kento , Yamada Shinya , Sangen Ryusho , Izumida Toshihide , Mori Hideyuki , Kiyosawa Jun , Saito Atsushi , Iguchi Masaharu , Nakahashi Takeshi , Kasamaki Yuji , Fukuda Akihiro , Kanda Tsugiyasu , Okuro Masashi
Published: November 2021

Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.

Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.

Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.

Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group.
Oral administration of East Asian herbal medicine for peripheral neuropathy
Authors: Lee Hoseok , Jo Hee-Geun , Lee Donghun
Published: November 2021

Background:

Peripheral neuropathy (PN) is one of the most common medical problems encountered. Since the pathophysiology and symptom manifestation characteristics of PN are very diverse, it is difficult to provide an appropriate treatment. East Asian herbal medicine (EAHM) has long contributed to the treatment of neurological and pain disorders. The goal of this systematic review is to measure the efficacy and safety of EAHM for PN and to identify core herb patterns. In order to derive a more conservative result, a random effect model will be applied regardless of the significance of heterogeneity.

Methods:

We will search 10 databases to identify suitable studies. There will be no restrictions regarding language or publication date. Primary outcomes will be nerve conduction velocity and response rate. Secondary outcomes will be any objective tool that can measure the efficacy of EAHM, and adverse events will be included. We will perform a meta-analysis of trials with the same intervention and outcome with comparator in a similar population. Meanwhile, in order to explore significant potential correlation in herb preparation, association rule analysis based on the Apriori algorithm will be performed on the collected composition data of herbal medicines.

Results:

This study will provide scientific evidence for the treatment of EAHM for PN.

Conclusions:

Based on the results of this review, it is expected that the efficacy and safety of EAHM for PN can be confirmed. In addition, through additional analysis using data mining techniques, it will be possible to present a core herb pattern related to this research topic.
Comparison of rehabilitation outcomes for transcatheter versus surgical aortic valve replacement as redo procedure in patients with previous cardiac surgery
Authors: Wang Guobin , Li Xuefeng , Zhang Zhaojie , Dong Jige
Published: November 2021

Background:

Currently, the number of severe aortic stenosis (AS) patients with a history of prior cardiac surgery (PCS) has increased. Both transcatheter aortic valve replacement (TAVR) and traditional surgical aortic valve replacement (sAVR) are effective therapy for AS. However, PCS increases the risk of adverse outcomes in patients undergoing aortic valve replacement. Thus, this meta-analysis was designed to comparatively evaluate the impact of PCS on clinical outcomes between TAVR and sAVR.

Methods:

A systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to February 1, 2021 was conducted for relevant studies that comparing TAVR and sAVR for severe AS patients with a history of PCS. The primary outcome was the non-inferiority of TAVR and sAVR in mortality. The secondary outcomes were the other clinical outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2.

Results:

A total of 11 studies including 8852 patients were identified. The pooled results indicated that there was no difference in 30-day, and 1-year all-cause mortality between TAVR and sAVR. No significant difference was also observed in total follow-up and cardiovascular mortality between TAVR and sAVR. However, subgroup analysis revealed significantly higher 1-year all-cause mortality (OR 1.92; 95% CI 1.05–3.52; P = .04) and total follow-up mortality (OR 2.28; 95% CI 1.09–4.77; P = .03) in TAVR than sAVR for patients with a history of coronary artery bypass graft, aortic valve replacement, and mitral valve reconstruction. In addition, TAVR experienced higher pacemaker implantation than sAVR. However, compared with sAVR, TAVR experienced shorter length of stay (MD –3.18 days; 95% CI –4.78 to –1.57 days) and procedural time (MD –172.01 minutes; 95% CI –251.15 to –92.88) respectively. TAVR also lead to much less bleeding than sAVR.

Conclusions:

Our analysis shows that TAVR as a redo procedure was equal to sAVR in mortality for severe AS patients with PCS, especially coronary artery bypass graft. We agree the advantage of TAVR as a redo procedure for patients with a history of PCS. Patients receiving TAVR experienced rapid recovery, shorter operation time and less bleeding, without increasing short and long term mortality.
Clozapine prescribing barriers in the management of treatment-resistant schizophrenia
Authors: Baig Anum Iqbal , Bazargan-Hejazi Shahrzad , Ebrahim Gul , Rodriguez-Lara Jaziel
Published: November 2021

Background:

Treatment-resistant schizophrenia is prevalent and difficult to manage, as patients fail multiple antipsychotic trials before being considered as treatment-resistant. Currently clozapine is the only Food and Drug Administration-approved pharmacotherapy for treatment-resistant schizophrenia but remains under-prescribed. The purpose of this study is to investigate recent literature on clozapine in order to identify barriers to prescribing clozapine and categorize the recommended solutions.

Methods:

We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using free text and the medical subject headings, we searched MEDLINE/PubMed electronic bibliographic database from 2017 until 2020. Eligible studies included peer-reviewed English language articles with multiple methodologies aiming to identify clozapine barriers in treatment-resistant schizophrenia. We used search terms combining clozapine AND treatment OR treatment-resistant schizophrenia AND barriers AND prescribing OR prescription OR prescriber. We merged search results in a citation manager software, removed duplicates, and screened the remaining articles based on the study eligibility criteria.

Results:

We retrieved 123 studies, however, only 10 articles exclusively met the study inclusion criteria for full text review. These studies represented 20 countries; 6 were exclusively conducted in the US. The top barriers delineated by the studies include: providers’ lack of knowledge and training (n = 7), concern about side effects (n = 8), and poor adherence (n = 7). All studies described more than 1 barrier. Other barriers included prescriber-perceived barriers (n = 4), administrative barriers (n = 5), and other healthcare systems-related barriers (n = 3). Top recommendations to overcome clozapine prescription barriers included improving prescriber clozapine education/training, utilizing interdisciplinary teams and providing integrated care via clozapine clinics, and simplifying blood test monitoring.

Conclusion:

Clozapine remains under-prescribed for patients with treatment-resistant schizophrenia due to multiple barriers related to the individual prescriber, system of care, and technology. It is recommended that by improving prescriber knowledge and training, use of integrated care, and use of technology that can enable continuous, real-time blood test monitoring, these barriers may be overcome.
Clinical therapeutic effects of pulsed-radiofrequency combined with blockade in the treatment of patients with chronic migraine
Authors: Zhang Guang-Zhi , Chen Yao
Published: November 2021

Background:

Recently, researchers have emphasised on the clinical therapeutic effects of pulsed-radiofrequency combined with blockade to treat chronic migraine (CM) patients. However, there are controversial results. Therefore, the authors conduct the proposed research to assess the efficacy of pulsed-radiofrequency combined with blockade to teat CM patients.

Methods:

The authors will perform a comprehensive literature search on the following online-based databases from establishment till October 2021: Web of Science, EMBASE, PubMed, China National Knowledge Infrastructure, the Cochrane library, and WanFang database. We will consider all randomized controlled trials of pulsed-radiofrequency combined with blockade for CM for inclusion. There won’t be any language constraints. Following the search, a pair of reviewers will independently screen and choose related articles to include in the meta-analysis. The Cochrane risk of bias tool will be used to assess the systematic value of all included randomized controlled trials. The study will utilize the risk ratio, mean differences, or standardized mean differences and their 95% confidence intervals to perform an estimation of the pooled mean effect size. Lastly, the authors will employ funnel plot, Egger test, and sensitivity analysis to determine and describe possible heterogeneity.

Results:

The authors will publish the results in a peer-reviewed journal.

Conclusion:

The proposed study will be the first to evaluate the effectiveness of pulsed-radiofrequency combined with blockade in the treatment of patients with CM.

Ethics and dissemination:

Since the proposed study is a systematic review of published studies, an ethics approval is not needed.

Registration number:

Oct 12, 2021.osf.io/d2wx3. (https://osf.io/d2wx3/).
East Asian herbal medicine for cancer pain
Authors: Jo Hee-Geun , Lee Donghun
Published: November 2021

Background:

Cancer pain is an important factor in cancer management that affects a patient's quality of life and survival-related outcomes. The aim of this review is to systematically evaluate the efficacy and safety of oral administration East Asian herbal medicine (EAHM) for primary cancer pain, and to explore core herb patterns based on collected data.

Methods:

A comprehensive literature search will be conducted in 10 electronic databases including PubMed, Cochrane Library, Cumulative Index to Nursing & Allied Health Literature, EMBASE, Korean Studies Information Service System, Research Information Service System Oriental Medicine Advanced Searching Integrated System, Korea Citation Index, Chinese National Knowledge Infrastructure Database (CNKI), CiNii for randomized controlled trials from their inception until August 19, 2021. Statistical analysis will be performed in the software R version 4.1.1. and R studio program using the default settings of the ‘meta’ package. When heterogeneity in studies is detected, the cause will be identified through meta regression and subgroup analysis. Methodological quality will be assessed independently using the revised tool for risk of bias in randomized trials (Rob 2.0).

Results:

This study will provide more comprehensive and specific evidence of EAHM for cancer pain management.

Conclusions:

Based on the results of this review, it is expected that the efficacy and safety of East Asian herbal medicine for cancer pain may be confirmed. In addition, it will be possible to derivation of a core herb pattern related to this research topic through additional association rule mining analysis.
Posterior instrumented fusion on lumbar stenosis syndrome can bring benefit to proximal degenerative kyphosis
Authors: Xu Shuai , Guo Chen , Liang Yan , Zhu Zhenqi , Zhang Hongguang , Liu Haiying
Published: November 2021

The effect on degenerative thoracolumbar kyphosis (DTLK) after short-segment instrument for lumbar spinal stenosis syndrome (LSS) remains controversial. Based on the biomechanics and compensatory of the global spino-pelvic alignment, it was assumed that the interference on the lumbar spine, instead of the thoracolumbar segment, could still make a difference on the proximal spine.

To explore whether DTLK could improve with only surgery for LSS and identify influencing factors on postoperative TLK.

The study was performed from January 2016 to December 2018. Sixty-nine participants (25 male) diagnosed LSS with DTLK were enrolled and surgery was only for LSS. Radiological parameters included TLK, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope, and osteoporosis. Clinical outcomes were visual analogue scale and Oswestry disability index. According to lower instrumented vertebrae (LIV) on L5 or S1, inter-group comparisons were performed between LIV on L5 (L5 group) and S1 (S1 group).

Demographics were well-matched between L5 and S1 group with a mean follow-up of 24.3 ± 12.1 (m). TLK improved with a mean of 16.2 ± 7.6 (°) (P < .001). There was no significance on radiological and clinical parameters between L5 and S1 groups except for a larger pelvic tilt in S1 group (P = .046). Visual analogue scale (P = .787) and Oswestry disability index (P = .530) were both indifferent between normal TLK and DTLK at last (P > .05). Postoperative TLK was affected by osteoporosis and sacral slope, the latter was dominated by pelvic incidence and pelvic rotation. Osteoporosis was the risk factor for TLK correction (P = .001, odd risk = 9.58).

DTLK decreased if instrument only performed for LSS, where TLK and clinical outcomes are comparably affected whether L5 or S1 is selected as LIV. This study supplements the compensatory mechanism of spino-pelvic alignment, especially for cases with severe osteoporosis.
Molecular characterization of hemoglobinopathies and thalassemias in Northern Guangdong Province, China
Authors: Ma Zhanzhong , Fan Shushu , Liu Jun , Liu Yulan , Guo Yanle , Huang Wenbo
Published: November 2021

To detect the molecular characterization of hemoglobinopathies and thalassemias in Northern Guangdong Province of China.

We recruited 10,285 subjects who were screened for hemoglobin (Hb) variants and thalassaemia genotypes in the outpatient department of Yuebei People's Hospital from January 2018 to December 2020. The subjects collected venous blood samples for blood cell parameter analysis and Hb electrophoresis analysis. When the average red blood cell volume is <82 fL, or the average red blood cell Hb is <27 pg, or HbA2 > 3.5%, or HbA2 < 2.5%, or HbF > 2.0%, the screening is positive if one of them is satisfied. All subjects who were screened positive were tested for the thalassaemia gene by gap-polymerase chain reaction, PCR-based reverse dot blot, and DNA sequencing.

Among all subjects screened, the overall prevalence of hemoglobinopathies and thalassemias were 0.46% (47/10,285) and 21.02% (2162/10,285) in Northern Guangdong Province. We found that Hb Q-Thailand is the most common, and other types of hemoglobinopathies are followed by Hb E, Hb New York, Hb G-Chinese, Hb G-Coushatta, Hb J-Bangkok, Hb J-Broussais, Hb Ottawa, and Hb G-Taipei. We identified 1340 cases (13.03%) of α-thalassemia, mainly includes --SEA deletion (71.64%), –α3.7 deletion (12.01%), –α4.2 deletion (4.78%). And identified 652 cases (6.34%) of β-thalassemia, the most prevalent being CD 41/42(-TTCT) (35.89%), IVS-II-654 (C > T) (33.44%), CD 17 (A > T) (10.28%) and –28(A > G) (9.66%). Furthermore, there are 170 cases (1.65%) of α combined β thalassaemia. In addition, we found a rare case with –80 (T > A) of β-thalassemia. The results of this study found a high prevalence of hemoglobinopathies and thalassemias in Northern Guangdong Province, China. There were some differences molecular characterizations of thalassemia in different areas of China.

Our results enriched the related information of hemoglobinopathies and thalassemias in the region, which provided valuable references for the prevention and control of thalassemia.