bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly accurate enzyme turnover number prediction and enzyme engineering with PreKcat
Authors: Yu Han , Deng Huaxiang , He Jiahui , Keasling Jay , Luo Xiaozhou
Published: May 2023

Prediction of enzyme turnover number (kcat) is essential for designing and optimizing enzymes for various biotechnological and industrial applications, but the limited performance of current prediction tools on diverse tasks hinders their practical applications. Here, we introduce PreKcat, a method based on pretrained language models for highly accurate kcat prediction from protein sequences and substrate structures. A two-layer framework derived from PreKcat was proposed to allow robust kcat prediction in considering environmental factors, including pH and temperature. In addition, four representative re-weighting methods were systematically explored to successfully reduce the prediction error in high kcat values prediction tasks. Furthermore, PreKcat showed strong generalizability in two extended tasks, Km and kcat / Km prediction. Using PreKcat, we achieve significant increases kcat and kcat / Km (approximately 7-fold and 3.5-fold, respectively) on one enzyme, the highest reported values to date. PreKcat is a valuable tool for deciphering the mechanisms of enzyme kinetics and enables novel insights into enzyme engineering and their industrial applications.
Ex-vivo Expansion of Bone Marrow-derived Mesenchymal Stromal Cells for Clinical Use: the Starting Platelet Concentration of Human Platelet Lysate Affects Cell Proliferation, Senescence and Phenotype
Authors: Becherucci Valentina , Nisticò Francesco , Piccini Luisa , Ceccantini Riccardo , Brugnolo Francesca , Ermini Stefano , Allegro Elisa , Bisin Silvia , Pavan Paola , De Rienzo Elena , Bindi Brbara , Cunial Vanessa , Astori Giuseppe , Bambi Franco
Published: May 2023

Background: In the last decades the replacement of fetal bovine serum (FBS) with human Platelet Lysate (hPL) for ATMPs expansion has been for a long time investigated to overcome FBS-related issues. Despite several studies confirming hPL safety and efficacy in Mesenchymal Stromal Cell (MSC) expansion, there are still gaps in the knowledge of hPL as a supplement, like the composition and release criteria. As growth factors are released after thrombocytes lysis during hPL production, starting platelet concentration may affect hPL quality. This study aimed to investigate hPL starting platelet concentration effects on bone marrow-derived MSC (BM-MSC) ex-vivo expansion.
Methods: MSC were isolated from the bone marrow (BM) of 7 donors and cultured from passage 1 to 5 in 4 different conditions: DMEM 10% FBS and DMEM 5% hPL varying starting platelet concentration. Particularly hPL was produced by in-hospital Transfusion Service, in three different starting platelet concentrations (sPLTC): high (4x109 PLTS/ml), medium (2x109 PLTS/ml) and low (1x109 PLTS/ml). The study focused on the analysis of parameters that are mostly affected by hPL such as cell proliferation, immunophenotype, telomeric length, differentiation and senescence.
Results: Evaluation of proliferation indexes (PDT and PD) underlined dose-dependent effects of sPLTC, also confirmed by flow cytometry cell cycle analysis. Immunophenotype seems not to be affected by sPLTC. Differences were instead detected by adhesion molecules markers CD10, CD106, CD166, and CD146 expression, as their expression showed a dose-dependent downregulation, based on the sPLTC. Differentiation potential seems to be unaffected by different sPLTC as all cell batches differentiated into osteoblasts, adipocytes and chondrocytes. On the contrary senescence and relative telomeric length RTL (detected by SA-β-GAL activity and PNA-FITC flow cytometry) are strongly affected by sPLTC, in a dose-dependent manner. Particularly high sPLTC results in cell senescence associated with decreased RTL.
Conclusions: our data showed that sPLTC affects some BM MSCs properties, underlying its importance during hPL preparation. According to this study, we suggest a medium sPLTC for hPL preparation, as the best compromise between the increase in proliferation index and effects on senescence.
SARS-CoV-2 antibodies recognize 23 distinct epitopic sites
on the receptor binding domain
Authors: Jiang Jiansheng , Boughter Christopher , Ahmad javeed , Natarajan Kannan , Boyd Lisa , Meier-Schellersheim Martin , Margulies David
Published: May 2023

The COVID-19 pandemic and SARS-CoV-2 variants have dramatically illustrated the need for a better understanding of antigen (epitope)-antibody (paratope) interactions. To gain insight into the immunogenic characteristics of epitopic sites (ES), we systematically investigated the structures of 340 Abs and 83 nanobodies (Nbs) complexed with the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein. We identified 23 distinct ES on the RBD surface and determined the frequencies of amino acid usage in the corresponding CDR paratopes. We describe a clustering method for analysis of ES similarities that reveals binding motifs of the paratopes and that provides insights for vaccine design and therapies for SARS-CoV-2, as well as a broader understanding of the structural basis of Ab-protein antigen (Ag) interactions.
Electrocardiographic Changes During Sustained Normobaric Hypoxia in Patients After Myocardial Infarction
Authors: Kramer Tilmann , Hoenemann Jan-Niklas , Weis Henning , Hoffmann Fabian , Rosenkranz Stephan , Baldus Stephan , Hellmich Martin , Levine Benjamin , Jordan Jens , Tank Jens , Limper Ulrich
Published: May 2023

Background
Whether physically fit patients who have recovered from myocardial infarction can safely stay and exercise at high altitude is unclear. Myocardial tissue hypoxia and pulmonary hypertension could affect cardiac function, electrophysiology and predispose to arrythmias.
Methods
We included four non-professional male athletes (57.8 ± 3.3 years). All were clinically stable 37 to 104 months after left ventricular ST-elevation myocardial infarction and subsequent drug-eluting stenting of single-vessel coronary artery disease. Oxygen was gradually decreased to a minimum of 11.8% followed by oxygen increase back to 20.9%. ECG, ergometry, and echocardiography were performed in normoxia and hypoxia.
Results
In hypoxia, ECG showed significant QTc interval prolongations using Bazett’s (402 ± 13 to 417 ± 25ms), Fridericia's (409 ± 12 to 419 ± 19ms), and Holzmann’s (103 ± 4 to 107 ± 6%) formula compared to normoxia. The response was partly reversed during recovery. Echocardiographic signs of pulmonary hypertension during normobaric hypoxia correlated significantly with altered QTc intervals (p < 0.001).
Conclusions
Even exceptionally healthy and fully revascularized patients post myocardial infarction may be susceptible to hypoxia-induced QTc prolongation and VES, particularly during physical exertion. Patients after myocardial infarction should be advised to seek consultation and examination by a cardiovascular specialist with expertise in high-altitude medicine prior to physical activities at high altitude.
Simultaneous Fractionation of Low-gluten Flour and Gum from Durian Seed: Process-Properties Relationship
Authors: Chew Zhi Ling , Kua Yin Leng , Gan Suyin , Tan Khang Wei , Lee Terri Zhuan Ean , Cheng Wai Kit , Lau Harrison Lik Nang
Published: May 2023

In this study, valuable low-gluten flour and gum were fractionated simultaneously from durian seed via a green and safe aqueous extraction method at maximum atom economy. As the extraction process significantly affected the properties and hence, the application of the flour and gum, the process-properties relationship of extraction temperature and W/S ratio were investigated and presented in this paper. The demucilaged durian seed flour (DDSF) and durian seed gum (DSG) solubilities and water absorption capacity (WAC) were found improved at higher extraction temperature (85 °C) due to bond cleavage and retention of amylose and hydrophilic amino acids. Furthermore, DSG with a solubility of 46.67% was the highest that can be achieved by current aqueous extraction method as further increase of W/S ratio and DSG yield exerted no effect on the solubility. Besides, the oil absorption capacity (OAC) of DSG was found higher than the DDSF due to the presence of nonpolar amino acids and fatty acids that tended to bind with the hydrophobic oil. OAC was mainly determined by the extraction yield and distribution of these hydrophobic fraction, instead of the degree of degradation. Higher overall yield was found at higher extraction temperature of 85 °C for simultaneous extraction of DDSF and DSG. While lower W/S ratio at 1:1 was preferable to obtain higher yield of DDSF, a higher W/S ratio at 5:1 was required for higher yield of DSG. Other than the extraction temperature, drying temperature and duration were key factors determining the colour of the extracted DDSF and DSG.
Risk of control failure to insecticides malathion, profenophos+cypermethrin mixture, and fipronil in boll weevil (Coleoptera: Curculionidae) populations from Bahia, Brazil
Authors: Coelho Beatriz Sousa , Leite Suzany Aguiar , Santos Mateus Pereira dos , Guedes Raul Narciso Carvalho , Bastos Cristina Schetino , Moreira Aldenise Alves , Bonfim João Evilásio Vasconcelos , Castellani Maria Aparecida
Published: May 2023

Background: To control the boll weevil Anthonomus grandis grandis (Coleoptera: Curculionidae), a key pest of cotton in the Americas, insecticides have been intensively used to manage their populations, increasing selection pressure for resistant populations. Thus, this study aimed detect insecticide resistance and assess insecticide control failure likelihhod of boll weevil populations exposed to malathion, profenophos+cypermethrin, and fipronil insecticides.
Results: Twelve populations of the boll weevil were collected from commercial cotton fileds of the state of Bahia, northeastern Brazil. These populations were exposed to malathion, profenophos+cypermethrin mixture and fipronil, at their respective maximum label dose for field applications. Three replicates of ten adult beetles were exposed to the insecticides and mortality was recorded 24 hours after exposure to the insecticides. The control failure likelihood was determined after 48 hours. The highest median lethal times (LT50) were observed for malathion and the profenophos+cypermethrin mixture. Resistance to at least one insecticide was detected in 11 populations; three populations were resistant to malathion and profenophos+cypermethrin; seven were resistant to all insecticides used. The resistance levels were low (<10-fold) for the three insecticides. Among 12 populations tested, 58% exhibited significant risk of control failure for the insecticide’s malathion and to profenophos+cypermethrin. The insecticide fipronil was efficient for the control of the boll weevil in 83% of the populations.
Conclusion: The results confirm the significant risk of insecticide control failure in the boll weevil populations to the main compounds used in the region. Thus, proper insecticide resistance management plans are necessary for the boll weevil in the region, particularly for malathion and fipronil insecticides.
Differential target multiplexed spinal cord stimulationusing a paddle-type lead placed at the appropriate site for neuropathic pain after spinal cord injury in patients with past spinal surgical histories: Study protocol for an exploratory clinical trial
Authors: Tanei Takafumi , Maesawa Satoshi , Nishimura Yusuke , Nagashima Yoshitaka , Ishizaki Tomotaka , Ando Masahiko , Kuwatsuka Yachiyo , Hashizume Atsushi , Kurasawa Shimon , Saito Ryuta
Published: May 2023

Background: Neuropathic pain after spinal cord injury (SCI), both traumatic and non-traumatic, is refractory to various treatments. Spinal cord stimulation (SCS) is one of the neuromodulation therapies for neuropathic pain, although SCS has insufficient efficacy for neuropathic pain after SCI. The reasons are presumed to be inappropriate locations of SCS leads and conventional tonic stimulation itself does not have a sufficient analgesic effect for the pain. In patients with past spinal surgical histories, the cylinder-type leads are likely to be placed on the caudal side of the SCI because of surgical adhesions. Differential target multiplexed (DTM) stimulation is one of the latest new stimulation patterns that is superior to conventional stimulation.
Methods: A single-center, open-label, randomized, two-way crossover trial is planned to investigate the efficacy of SCS using DTM stimulation placing a paddle lead at the appropriate site for neuropathic pain after SCI in patients with spinal surgical histories. The paddle-type lead delivers energy more efficiently than a cylinder-type lead. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). The primary outcome is rates of achieving pain improvement with more than 33% reduction 3 months after SCS system implantation. The secondary outcomes are to be evaluated as follows: 1) effectiveness of DTM and tonic stimulations during the SCS trial; 2) changes of assessment items from 1 to 24 months; 3) relationships between the result of the SCS trial and the effects 3 months after SCS system implantation; 4) preoperative factors associated with a long-term effect, defined as continuing for more than 12 months; and 5) whether gait function improves from 1 to 24 months.
Discussion: A paddle-type lead placed on the rostral side of SCI and using DTM stimulation may provide significant pain relief for patients with intractable neuropathic pain after SCI in patients with past spinal surgical histories.
Trial registration: Japan Registry of Clinical Trials (jRCT) jRCT 1042220093. Registered on 6 January 2023. jRCT is approved as a member of the Primary Registry Network of WHO ICTRP.
Mixed-method study on the effects of conditional cash transfer program on the under- and overnutrition in children and adolescents: a school-based evidence from Caraga Region, the Philippines
Authors: Herrera Deborah Jael , Herrera Miraluna , Amora Donnacham , Bas Sherlyn , Miranda Caryl Aya , Hal Guido Van
Published: May 2023

Background This study aimed to determine the effects of Pantawid Pamilyang Pilipino Program (4Ps), a CCT program in the Philippines, on the multiple faces of malnutrition in children and adolescents and examine the perceptions and experiences of parents and other stakeholders on how 4Ps influenced child nutrition.Methods A concurrent mixed-method study was conducted in Caraga Region, the Philippines. Quantitative study utilized 5541 school-based data on child nutrition, socio-demographic and -cultural profiles, and inclusion to 4Ps from 10 representative schools in 4 school divisions. Associations between child nutritional status and inclusion to 4Ps, socio-demographic and -cultural factors, and their interactions were tested using the multilevel mixed-effect logistic models with school and year random effects. The qualitative study, on the other hand, was concurrently conducted through eight (8) focused group discussions (FGDs) cumulating 33 participants to enable triangulation and an in-depth description of the findings. A constructivist grounded theory analytical approach with four-level analysis was performed including identifying text, coding, and developing themes and theoretical framework.Results The likelihood of stunting was lower among 4Ps children (AOR: 0.70, 95%CI: 0.52–0.93) compared with non-4Ps children. Ethnicity was associated with higher odds of stunting among indigenous children from major tribes (AOR: 1.67, 95%CI: 1.08–2.47) compared with non-indigenous children. However, inclusion in the 4Ps has no significant effect on children's concurrent undernutrition and overnutrition. Interactions were found between inclusion to 4Ps and locality, with higher odds of stunting among 4Ps children in Agusan del Sur (AOR = 2.45, 95%CI:1.40–4.30) compared with 4Ps children in Agusan del Norte. Finally, qualitative findings revealed the positive and negative effects of 4Ps on malnutrition which were strongly influenced by parenting styles, parents’ attitudes towards cash grants and cash card management, provisions of child nutrition interventions, and delivery conditions of 4Ps.Conclusions Improving children's nutrition is bolstered in the 4Ps implementation strategies. Targeted strategies to prevent the negative implications of a cash grant and card mismanagement should be considered by policymakers and implementers for a scaled-up impact in decreasing malnutrition in children.
Prognostic value of pathogenic variants in Lafora Disease: systematic review and meta-analysis of patient-level data.
Authors: Pondrelli Federica , Minardi Raffaella , Muccioli Lorenzo , Zenesini Corrado , Vignatelli Luca , Licchetta Laura , Mostacci Barbara , Tinuper Paolo , Kooi Craig W. Vander , Gentry Matthew S. , Bisulli Francesca
Published: May 2023

Background: Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of genetic factors on disease progression has yet to be confirmed. We present a systematic review and meta-analysis of the known pathogenic variants to identify genotype-phenotype correlations.
Methods: We collected all reported cases with genetically-confirmed LD containing data on disease history. Pathogenic variants were classified into missense (MS) and protein-truncating (PT). Three genotype classes were defined according to the combination of the variants: MS/MS, MS/PT, and PT/PT. Time-to-event analysis was performed to evaluate survival and loss of autonomy.
Results: 250 cases described in 70 articles were included. The mutated gene was NHLRC1in 56% and EPM2A in 44% of cases. 114 pathogenic variants (67 EPM2A; 47 NHLRC1) were identified. The NHLRC1 genotype PT/PT was associated with shorter survival [HR 2.88; 95%CI 1.23-6.78] and a trend of higher probability of loss of autonomy [HR 2.03, 95%CI 0.75-5.56] at the multivariable Cox regression analysis. The population carrying the homozygous p.Asp146Asn variant of NHLRC1genotype wasconfirmed to have a more favourable prognosis in terms of disease duration.
Conclusions: This study demonstrates the existence of prognostic genetic factors in LD, namely the genotype defined according to the functional impact of the pathogenic variants. Although the reasons why NHLRC1 genotype PT/PT is associated with a poorer prognosis have yet to be fully elucidated, it may be speculated that malin plays a pivotal role in LD pathogenesis.
Participatory Logic Modeling in a Multi-Site Initiative to Advance Implementation Science
Authors: Easterling Douglas , Jacob Rebekah R. , Brownson Ross C. , Haire-Joshu Debra , Gundersen Daniel A. , Angier Heather , DeVoe Jennifer E. , Likumahuwa-Ackman Sonja , Vu Thuy , Glasgow Russell E. , Schnoll Robert
Published: May 2023

Background: It is increasingly being recognized that logic models should be developed through a participatory approach which allows input from those who carry out the program being evaluated. While there are many positive examples of participatory logic modeling, funders have generally not used this approach in the context of multi-site initiatives. This article describes an instance where the funder and evaluator of a multi-site initiative fully engaged the funded organizations in developing the initiative logic model. The focus of the case study is Implementation Science Centers in Cancer Control (ISC3), a multi-year initiative funded by the National Cancer Institute (NCI).
Methods: The case study was collectively constructed by representatives of the seven centers funded under ISC3. Members of the Cross-Center Evaluation (CCE) Work Group jointly articulated the process through which the logic model was developed and refined. Individual Work Group members contributed descriptions of how their respective centers reviewed and used the logic model. Cross-cutting themes and lessons emerged through CCE Work Group meetings and the writing process.
Results: The initial logic model for ISC3 changed in significant ways as a result of the input of the funded groups. Authentic participation in the development of the logic model led to strong buy-in among the centers, as evidenced by their utilization. The centers shifted both their evaluation design and their programmatic strategy to better accommodate the expectations reflected in the initiative logic model.
Conclusions: The ISC3 case study provides a positive example of how participatory logic modeling can be mutually beneficial to funders, grantees and evaluators of multi-site initiatives. Funded groups have important insights about what is feasible and what will be required to achieve the initiative’s stated objectives. They can also help identify the contextual factors that either inhibit or facilitate success, which can then be incorporated into both the logic model and the evaluation design. In addition, when grantees co-develop the logic model, they have a better understanding and appreciation of the funder’s expectations, and thus are better positioned to meet those expectations.
Identifying a key spot for mediator-interaction to tailor CO dehydrogenase’s affinity
Authors: Kim Suk Min , Kang Sung Heuck , Lee Jinhee , Heo Yoonyoung , Hwang Ho Won , Poloniataki Eleni G. , Yoon Hye-Jin , Lee Hyung Ho , Kim Yong Hwan
Published: May 2023

Fe‒S cluster-harboring enzymes, such as carbon monoxide dehydrogenases (CODH), employ sophisticated artificial electron mediators like viologens to serve as potent biocatalysts capable of cleaning-up industrial off-gases at stunning reaction rates. Unraveling the interplay between these enzymes and their associated mediators is essential for improving the efficiency of CODHs. Here we show the electron mediator-interaction site on ChCODHs (Ch, Carboxydothermus hydrogenoformans) using a systematic approach that leverages the viologen-reactive characteristics of superficial aromatic residues. By enhancing mediator-interaction (R57G/N59L) near the D-cluster, the strategically tailored variants exhibited a ten-fold increase in ethyl viologen affinity relative to the wild-type without sacrificing the turn-over rate (kcat). Viologen-complexed structures revealed the pivotal positions of surface phenylalanine residues, serving as external conduits for the D-cluster. One variant (G57/L59/W559) could treat a broad spectrum of waste gases (from steel-process and plastic-gasification) containing O2. Decoding mediator interactions will facilitate the development of industrially high-efficient biocatalysts encompassing gas-utilizing enzymes.
Characterization of Antimicrobial Peptide Produced by Bacillus Subtilis Subsp. Subtilis
Authors: ALAJLANI MUAAZ
Published: May 2023

Purpose: Antimicrobial peptides are amongst the most promising class of peptides to contract the rise of global antimicrobial resistant. This article investigates a new antimicrobial peptide from bacteria.Methods: Bacterial identification was based on phenotypical and biochemical properties as well as 16S rRNA gene sequence homology. Bacterial growth and production of the inhibitory substance was standardized and optimized. The newly antimicrobial peptide was purified to homogeneity, subsequently analyzed by PAGE and MALDI-TOF-MS.Results: The bacterium identified as Bacillus subtilis subsp. subtilis and designated as strain MZ-32. Landy medium was best for the production when compared with different media after fixing the least influential variables in standardized fermentation conditions. Carbohydrate and nitrogen supplements investigated to improve production in Landy medium. The antimicrobial peptide of 2.158-Da was active against a broad range of skin-born pathogenic bacteria that were resistant to standard antibiotics, and possessed the physico-chemical properties of an ideal antimicrobial agent in terms of water solubility, thermal resistance, and stability towards acid/alkali (pH 4.0 to 9.0) treatments.Conclusion: The new strain and its associated peptide are potentially new candidates for medical and biotechnological applications.
Patient-Reported Impact of Symptoms in Adrenoleukodystrophy (PRISM-ALD)
Authors: Varma Anika , Weinstein Jennifer , Seabury Jamison , Rosero Spencer , Dilek Nuran , Heatwole John , Engebrecht Charlotte , Khosa Shaweta , Chung Kaitlin , Paker Asif , Woo Amy , Brooks Gregory , Beals Chan , Gandhi Rohan , Heatwole Chad
Published: May 2023

Background
Adrenoleukodystrophy (ALD) is a multifaceted, x-linked, neurodegenerative disorder that affect patients through a variety of physical, emotional, social, and other disease-specific factors that collectively contribute to disease burden. Adrenomyeloneuropathy (AMN) is one of the most frequent clinical manifestations and a subset of ALD. To facilitate clinical care and research, it is important to identify which symptoms are most common and relevant to individuals with ALD and AMN.
Methods
We conducted semi-structured qualitative interviews and an international cross-sectional study to determine the most prevalent and important symptoms of ALD and AMN. Our studies included adult participants with a diagnosis of ALD and AMN who were recruited from national and international patient registries. Responses were categorized by age, sex, functional status, and other demographic and clinical features.
Results
Seventeen individuals with ALD and AMN participated in qualitative interviews, providing 1,709 direct quotes regarding their symptomatic burden. One hundred and nine individuals participated in the cross sectional survey study, which inquired about 182 unique symptoms representing 24 distinct symptomatic themes. The symptomatic themes with the highest prevalence in the ALD and AMN sample cohort were problems with balance (90.9%), limitations with mobility or walking (87.3%), fatigue (86.4%), and leg weakness (86.4%). The symptomatic themes with the highest impact scores (on a 0–4 scale with 4 being the most severe) were trouble getting around (2.35), leg weakness (2.25), and problems with balance (2.21). A higher prevalence of symptomatic themes was associated with functional ability, employment disruption, and speech status.
Conclusions
There are many patient-relevant symptoms and themes that contribute to disease burden in individuals with ALD and AMN. These symptoms, identified by those diagnosed with ALD and AMN, present key targets for further research and therapeutic development.
Near Real-time Detection and Moment Tensor Inversion of the May 11, 2022, Dharchula Earthquake
Authors: Kumar Pankaj , Silwal Vipul , Mahanta Rinku , Maurya Vipin Kumar , Sharma Mukat Lal , Kamal Kamal , Ammani Ambikapathy
Published: May 2023

On May 11, 2022, an Mw-5.2 earthquake occurred in the Dharchula region of Uttarakhand Himalayas, India. The Uttarakhand State Earthquake Early Warning System (UEEWS) detected and transmitted the warning within 13.61 seconds of the origin, taking only 6.25 seconds for processing, location and magnitude estimation, and warning dissemination. The complete analysis is performed using three seconds of waveforms. Using the initial earthquake parameters provided by the UEEWS, moment tensor inversion is performed using broadband seismometer network installed in northern India. The moment tensor (MT) inversion has been performed for the event using both the body waves and the surface waves. The paper discusses the importance of real-time event detection and efforts towards real-time MT source inversion of earthquakes in the Uttarakhand Himalayas.
A Dynamic Theory of the Feldstein–Horioka Puzzle: A New Measure of Home Country Bias
Authors: Takahashi Harutaka
Published: May 2023

The recent home country bias is primarily related to the home bias of equities as measured by the international Capital Asset Pricing Model (CAPM). This measure has declined over the past two decades amid financial globalization but remains high in most developed countries. The key to understanding this puzzling phenomenon lies in how accurately this indicator can be predicted. For example, a major drawback of the equity home bias indicator is that it cannot be applied to portfolios that span a broad menu of assets, including stocks, bonds, and bank loans. We propose an aggregate home bias indicator associated with savings retention rate (called "beta"), which is estimated by a Feldstein-Horioka regression. Note that domestic savings consist of a variety of assets. However, a drawback of the beta is that it is subject to variety of estimation biases. To avoid this problem, we re-estimate beta based on the saddle-path dynamics of investment under convex adjustment costs based on Tobin's q theory, an approach quite different from previous studies related to the Feldstein-Horioka puzzle (FHP). In doing so, we applied dynamic panel estimation to measure the impact of changes in domestic savings on investment behavior. The main empirical results are as follows. Home bias declined steadily from 0.57 to 0.32 through 2000, and the correlation between investment and savings disappeared from 2000 to 2008, but recovered to 0.5, the average of the 40-year home bias measure, after the 2008 financial crisis. Interestingly, after the financial crisis, people expected the home bias to be very high, but in fact it simply returned to the average level. The paper will focus only on the precise estimation of β and leave the causes of this phenomenon to other studies.
JEL: C23, F21, F32
Opioid Prescribing for Acute Postoperative Pain: An Overview of Systematic Reviews
Authors: McCorquodale Cara Louise , Greening Rachel , Tulloch Ross , Forget Patrice
Published: May 2023

Background
National guidelines for rational opioid prescribing for acute postoperative pain are needed to optimise postoperative pain control and function whilst minimising opioid-related harm.
Objectives
This overview of systematic reviews aims to summarise and critically assess the quality of systematic reviews related to the 20 previously published recommendations (ten relevant at patient and prescriber levels and ten at a system / Public Health level). It also aims to identify gaps in research that require further efforts to fill these in order to augment the evidence behind creating national guidelines for rational opioid prescribing for acute postoperative pain.
Methods
A systematic database search using PubMed/MEDLINE and Cochrane was conducted in November 2022. Furthermore, reference lists were reviewed. All identified systematic reviews were assessed for eligibility. Data from each study was extracted using a pre-standardised data extraction form. The methodological quality of the included reviews was assessed by two independent reviewers using the AMSTAR 2 checklist. Descriptive synthesis of the results was performed.
Results
A total of 12 papers were eligible for analysis. Only eight out of the total 20 prioritised recommendations had systematic reviews that provided evidence related to them. These systematic reviews were most commonly of critically low quality.
Conclusion
The consensus papers provide guidance and recommendations based on the consensus of expert opinion that is based on the best available evidence. However, there is a lack of evidence supporting many of these consensus statements. Efforts to further analyse interventions that aim to reduce the rates of opioid prescribing and their adverse effects should therefore continue.
Injectable hydrogel electrodes as conduction highways to restore native pacing
Authors: Rivera Gabriel Rodriguez , Post Allison , John Mathews , Buchan Skylar , Beranrd Drew , Razavi Mehdi , Cosgriff-Hernandez Elizabeth
Published: May 2023

There is an urgent clinical need for a preventative treatment regimen that addresses the underlying pathophysiology of ventricular arrhythmias, the leading cause of sudden cardiac death. The current report describes a new approach in cardiac rhythm management that leverages the native coronary anatomy for creation of flexible electrodes to directly and uniformly stimulate mid-myocardial tissues. Successful in vivo deployment of an injectable hydrogel electrode was achieved in a pig model via the rapid, in situ gelation of the two component hydrogel precursors to transform the vein into a flexible electrode with access far more refined than any current technologies allow. In addition to successful capture and pacing of the heart, analysis of surface ECG tracings and three-dimensional electroanatomic mapping revealed a QRS morphology comparable to native sinus rhythm, strongly suggesting the hydrogel electrode captures the deep septal bundle branches and Purkinje fibers. In an ablation model, electroanatomic mapping data demonstrated that the activation wavefront from the hydrogel reaches the mid-myocardium and endocardium much earlier than current single-point pacing modalities. Such uniform, controlled activation of broad swaths of tissue with wavefront propagation from the hydrogel electrode enables a unique opportunity to minimize the delayed myocardial conduction of heterogeneous tissue that underpins re-entry. Chronic studies using a pig model confirmed safety with absence of myocardial necrosis or retention of myocardial function. Collectively, these studies demonstrate the feasibility of a new pacing modality that most closely resembles native conduction with the potential to eliminate lethal re-entrant arrhythmias and provide painless defibrillation.
Fault modeling around Southern Anatolia using aftershock sequence of Maraş earthquakes (Mw=7.7 and Mw=7.6) and interpretation of potential field data
Authors: Büyüksaraç Aydın , Bektaş Özcan , Alkan Hamdi
Published: May 2023

On 6 February 2023, southeastern Turkey experienced devastating doublet earthquakes (Mw = 7.7 and Mw = 7.6) with a series of aftershocks along the East Anatolian fault zone. The main shocks were followed by ~ 15.000 aftershocks that are mainly distributed along the NNE-SSW direction, including ~ 400 events Mw ≥ 4.0 in the first 30 days. Although many moderate to large earthquakes occurred in the historical and instrumental periods in this region, these double earthquakes with aftershocks caused major impacts on life and released great seismic energy. In this study, we interpreted the gravity-magnetic data and the epicenter and hypocenter distribution of aftershocks to correlate the tectonic structures and the active fault zones. The results of potential field anomalies reveal the rotational anomalies in the southwestward direction associated with the tectonics structure of Anatolia. Further, shallow aftershocks are associated with high gravity anomalies, whereas in deeper depth gravity values demonstrated low anomalies. Finally, the findings of gravity-magnetic anomalies and aftershock sequences present that the first mainshock occurred in the unbroken segment of the East Anatolian fault zone.
A recommended testing region in MLH1 promoter for methylation detection in colorectal cancer patients
Authors: Tan Xiaoli , Fang Yongzhen , Fan Xinjuan , Deng Weihao , Huang Jinglin , Cai Yacheng , Zou Jiaxin , Chen Zhiting , Lin Hanjie , Xu Liang , Wang Guannan , Zhan Huanmiao , Huang Shuhui , Fu Xinhui
Published: May 2023

Background:Lynch syndrome screening should includeMLH1promoter methylation detection in patients with deficiency of MLH1 (dMLH1) in colorectal cancer, but there is still no consensus on the CpG detection sites. The aim of this study is to analyze the correlation between the specific CpG sites ofMLH1promoter and dMLH1 in a large sample, and to find the best detection region.Methods:Immunohistochemistry (IHC) was used to detect DNA mismatch repair (MMR) protein in patients with colorectal cancer (CRC), and bisulfite sequencing PCR (BSP) was used to detectMLH1promoter methylation.MLH1promoter was divided into 5 regions: region A (-755 to -574, relative to the start codon), region B (-597 to -393), region C (-420 to -188), region D (-286 to -53) and region E (-73 to +86), which were tested respectively. The correlation between methylation in each region and MLH1 expression was analyzed. The sample size was gradually expanded to 626 cases for testing the highest correlation region. Subsequently, the correlation betweenMLH1promoter methylation and clinical parameters was analyzed, and a nomogram model for the prediction ofMLH1promoter methylation was established. Survival analysis was performed to analyze the influence ofMLH1promoter methylation on the prognosis of CRC.Results:Thepvalues of correlation between methylation in five regions( regions A, B, C, D, and E) and MLH1 protein expression were 0.070, 0.070, 0.005, 0.002 and 0.002, respectively. Regions D and E were consistent. In the cohort of 626 cases, methylation in region E was significantly correlated with the female, family history, mutantBRAFV600E, dMLH1 and deficiency of PMS2 (dPMS2). The consistency of the nomogram model we established to predictMLH1methylation and BSP was 78.6%. And the sensitivity and specificity of this nomogram model were 97.5% and 72.8%, respectively. In this article, we found thatMLH1promoter methylation had no significant effect on the prognosis of CRC.Conclusions:In colorectal cancer, the CpG sites in the region E of theMLH1promoter are recommended to determine the status ofMLH1methylation. The nomogram model ofMLH1promoter methylation is valuable and reliable for predictingMLH1methylation status.
Does social media have any influence on perceived dental appearance? A cross sectional survey
Authors: Khalid Mariya , Ihsan Sarah , Habib Sana , Khan Ehtesham , Mian Hamad , Wazir Hanifullah , Khalid Zarlasht , Gilani Imran , Chughtai Mohammad Ali
Published: May 2023

Objectives:
To evaluate the impact of social media on perceived dental appearance and to determine the correlation between time spent on social media and its impact on perceived dental appearance.
Methodology:
It was a cross-sectional study based on web-based survey. A surveying tool was developed comprising questions about sociodemographic details, use of social media and its effect on perception of an individual regarding his/ her dental appearance. The number of responses received were 347 in a period of three months. Scores were given to variables of Confidence, depression, participation in social gatherings, being ignored socially and being bullied because of dental appearance. These scores were added and final score was categorized from “less than 0 (<0)” as negative and “Greater than 0 (>0)” as positive impact.
Results:
Among 347 participants, 38% were males and 62% were females. Regarding perceived dental appearance, social media had positive impact on 310(89.3%) of participants and had negative impact on 37(10.7 %) of participants. No correlation was found between time spent on social media and impact on perceived dental appearance with P value statistically non-significant.(P value: 0.477)
Conclusion:
Majority of participants reported to have a positive impact of social media on perceived dental appearance. No statistically significant correlation was found between time spent on social media and its impact on perceived dental appearance.
CD4, CD20 and PD-L1 as a marker of recurrence in non-muscle invasive bladder cancer
Authors: Semeniuk-Wojtaś Aleksandra , Modzelewska Magdalena , Poddębniak-Strama Karolina , Kołaczyńska Sylwia , Lubas Arkadiusz , Górnicka Barbara , Jakieła Anna , Stec Rafał
Published: May 2023

Introduction

A tumor microenvironment plays an important role in bladder cancer development as well as in a treatment response.

Purpose

The aim of the study is to assess how the components of the microenvironment, in terms of cells, potentially affect tumor recurrence as well as to find the potential biomarkers for immunotherapy in NMIBC.

Methods

The study group consisted of 55 patients with primary NMIBC. Immunohistochemistry was performed on sections of primary papillary urothelial carcinoma of the bladder removed during transurethral resection of the tumor. Cox proportional hazard multiple regression analysis was performed to characterize tumors with the highest probability of an unfavorable outcome.

Results

The expression of analyzed variables was found in 90% of the examined tissues. Multivariate analysis confirmed that the CD4 (HR 1.19, 95% CI 1.07-1.32, p = 0.001), CD20 (HR 0.9, 95% CI 0.84-0.97, p = 0.008) and PD-L1 expressed on tumor cells (HR 0.05, 95% CI 0.008-0.29, p = 0.01) were independently associated with the risk of recurrence of bladder cancer. Patients with weak CD4+ cells (< 4,6%) infiltration and severe CD20+ infiltration (>10%) belong to the group with a lower risk of recurrence. The cancer in this group frequently recurs also after 12 months (p=0.0005).

Conclusions

The evaluation of CD4+ and CD20+ cells in the tumor microenvironment, in addition to PD-L1 on tumor cells, facilitates determination of a group of patients with a low risk of the recurrence that could also be recognized after 12 months following the primary tumor resection.
The impact of Indoor Residual Spraying (IRS) withdrawal in the Lake Zone Regions in Mainland Tanzania. Should Tanzania withdrawal its IRS program?
Authors: Mwalimu Charles D , Lazaro Samwel N , Kisinza William N , Magesa Stephen M , Kiware Samson S
Published: May 2023

Background: Indoor Residual Spray (IRS) has proven to be one of the most effective malaria vector control interventions in reducing malaria transmission mainly in areas with high transmission. With the support from the US President’s Malaria Initiative (PMI), Tanzania has gone through expansion of IRS implementation with different insecticides from one district in 2007 to 18 districts in 2012. However, due to financial constraints this was followed by IRS withdrawal to 6 districts by 2021 - with planned further withdrawal in 2022 – 2023 down to 2 districts.
Method: The retrospective analysis is performed to understand the impact of IRS withdrawal based on DHIS2 malaria incidence per 1000 population data. Data is subjected to interrupted time series (ITS) based on monthly periods to investigate whether the effect due to IRS withdrawal is statistically significant or not. The analysis helps to examine the changes in level and/or trend before, during, and after IRS withdrawal.
Results: Visual inspections on yearly time series plots indicate that withdrawing IRS after one, two, three, or even four rounds of IRS implementation results into resurgence of malaria incidence.
The interrupted time series statistical model results based on monthly data show that the difference between the trend during IRS and after withdrawal is negative and statistically significant (p < 0.001) indicating that monthly malaria incidence decreases over time during IRS. The immediate effect after the IRS is withdrawn is positive and statistically significant (p < 0.001), indicating that withdrawing IRS resulted in increased malaria incidence. The sustained effect after IRS withdrawal is positive and statistically significant (p < 0.001), indicating that each day that passes after IRS is withdrawn, the malaria incidence increases. Overall, malaria resurgence is observed in almost all the districts in which IRS was prematurely withdrawn. Such malaria rebounds costs human lives and therefore may go beyond epidemiological concerns, raising ethical, moral and human rights issues.
Conclusion: Any decision to withdrawal IRS should ensure its replacement with an equally effective or superior intervention. There is currently no data to support that the new nets being rolled-out in the country are suitable alternatives to IRS; especially in areas of high malaria transmission with reported insecticide resistance. This calls for a need for endemic countries to continue collecting data in local setting on the performance of current and forthcoming “new net” products to ascertain their suitability to replace IRS.
Systemic and cyber-physical methodology for the implementation of Industry 4.0 in Mexican companies of the automotive manufacturing industry
Authors: Romeo Lorenzo Lázaro González , Reyes Juan Bory , Ramírez Jorge A. Rojas
Published: May 2023

The transition towards the new technological paradigm in production systems resulting from Industry 4.0 (hereinafter I4.0), pursues among its main objectives, greater operational efficiency, and productivity, a greater scope of automation, customization, and flexibility in production, the increase in man-machine interaction, as well as the creation of more complex but better-paid jobs and new business models. For this reason, a broad understanding of what constitutes I4.0 today and what can represent the future requires knowledge about the technologies that make it up, as well as different tools that can help to carry out a correct and comprehensive implementation. The relevance of the Mexican automotive manufacturing industry in the national economy, as well as the importance of the I4.0 transition in this sector, is addressed, referring to several success stories and their key factors. A Systemic and Cyber-physical Methodology is presented as a fundamental component of this work, where its different stages are described, the used tools, and its isomorphic relationship with the Soft Systems Methodology. As an added element an illustrative example is provided of how the application of the Proposed Methodology would be in an Automotive Manufacturing Company.
Clinical diagnosis and treatment of prostate basal cell carcinoma: A case report and literature review
Authors: Xu Yan , Xiao Jun , Wang Zhaohui , Shen Zhou , Liu Yixun , Xu Congyun , Huang Tao
Published: May 2023

Background: Prostate basal cell carcinoma (BCC) is a rare pathological type of prostate cancer, representing only <0.01% of malignant prostate tumors.
Case presentation: A 73-year-old male patient presented to The First Affiliated Hospital of the University of Science and Technology of China (USTC) on December 28, 2020. The patient developed perineal dull pain and discomfort 15 years earlier, without obvious accompanying symptoms. The patient underwent multiple punctures and transurethral resection of the prostate (TURP), but no marked cancerization was noted, and the pain gradually worsened. Finally, puncture biopsy in the present hospital suggested BCC/adenoid cystic carcinoma (ACC) of the prostate. Pathology showed that the nuclei were relatively uniform, and the cytoplasm was scarce. Large, nested foci were observed accompanied by palisade arrangement of the surrounding cells, with necrosis in the center. Basaloid cells were irregularly arranged with small to medium solid nests. Stripes or small tubular structures were occasionally seen in which eosinophils were present. Nuclear division was rare. Based on histology and immunohistochemistry, the patient was diagnosed with prostate BCC/ACC. Because the patient had multiple distant metastases, surgery could not be performed. Hormonal therapy was performed. The patient died of bowel obstruction, intestinal perforation, and severe abdominopelvic infection 3 months later.
Conclusions: Prostate BCC is a rare prostate malignant tumor, with apparently latent manifestations in the early stage and no increase in prostate-specific antigen. Therefore, it could be easy to be ignored or missed. Furthermore, biological behaviors vary, and multiple metastases in the late-stage lead to a poor prognosis.