bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity of CFTR variants across ancestries characterized using 454,727 UK biobank whole exome sequences
Authors: Ideozu Justin E. , Liu Mengzhen , Riley-Gillis Bridget M. , Paladugu Sri R. , Rahimov Fedik , Krishnan Preethi , Tripathi Rakesh , Dorr Patrick , Levy Hara , Singh Ashvani , Waring Jeffrey F. , Vasanthakumar Aparna
Published: March 2024

Background

Limited understanding of the diversity of variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene across ancestries hampers efforts to advance molecular diagnosis of cystic fibrosis (CF). The consequences pose a risk of delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing the spectrum of CFTR variants across ancestries is critical for revolutionizing molecular diagnoses of CF.

Methods

We analyzed 454,727 UK Biobank (UKBB) whole-exome sequences to characterize the diversity of CFTR variants across ancestries. Using the PanUKBB classification, the participants were assigned into six major groups: African (AFR), American/American Admixed (AMR), Central South Asia (CSA), East Asian (EAS), European (EUR), and Middle East (MID). We segregated ancestry-specific CFTR variants, including those that are CF-causing or clinically relevant. The ages of certain CF-causing variants were determined and analyzed for selective pressure effects, and curated phenotype analysis was performed for participants with clinically relevant CFTR genotypes.

Results

We detected over 4000 CFTR variants, including novel ancestry-specific variants, across six ancestries. Europeans had the most unique CFTR variants [n = 2212], while the American group had the least unique variants [n = 23]. F508del was the most prevalent CF-causing variant found in all ancestries, except in EAS, where V520F was the most prevalent. Common EAS variants such as 3600G > A, V456A, and V520, which appeared approximately 270, 215, and 338 generations ago, respectively, did not show evidence of selective pressure. Sixteen participants had two CF-causing variants, with two being diagnosed with CF. We found 154 participants harboring a CF-causing and varying clinical consequences (VCC) variant. Phenotype analysis performed for participants with multiple clinically relevant variants returned significant associations with CF and its pulmonary phenotypes [Bonferroni-adjusted p < 0.05].

Conclusions

We leveraged the UKBB database to comprehensively characterize the broad spectrum of CFTR variants across ancestries. The detection of over 4000 CFTR variants, including several ancestry-specific and uncharacterized CFTR variants, warrants the need for further characterization of their functional and clinical relevance. Overall, the presentation of classical CF phenotypes seen in non-CF diagnosed participants with more than one CF-causing variant indicates that they may benefit from current CFTR modulator therapies.
Deficiency of peripheral CLA+ Tregs and clinical relevance in Behcet’s syndrome
Authors: Li Jiachen , Sun Feng , Zhu Danxue , Hou Yuke , Cheng Gong , Wang Ping , Jin Xu , Zhou Wenyan , Sun Xiaolin , Li Zhanguo , Liu Tian
Published: March 2024

Background

Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS.

Methods

We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs.

Results

The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA+ Treg cell deficiency. A decreased proportion of CLA+ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA+ Tregs in patients with BS increased with corticosteroids and immunosuppressants.

Conclusion

CLA+ Tregs decrease in association with arterial aneurysm in patients with BS. CLA+ Tregs may be a predictor of response to BS treatment.
Diagnostic dilemma in maxillofacial pathologies: a case series
Authors: Sarda Pavithra , Gurram Prashanthi , Ramakrishnan Karthik , Narayanan Vivek , Chandran Saravanan , Vinayachandran Divya
Published: March 2024

Background

Head and neck are a site of numerous pathologies with different aetiologies and presentations. Rare pathologies, although infrequent still do exist. Diagnostic dilemma in maxillofacial pathologies can be the most challenging situation. Dealing with uncertainty, although difficult, is a reality in surgical practice. Being thorough, attentive to details and clues, and maintaining an open mind are critical strategies in the approach to such a patient.

Case presentation

In our paper we are reporting a spectrum of 4 unusual variants of head and neck pathologies, whose age and sex were 52 years/ M, 37 years/F, 41 years/ F, 30 years/F respectively. All the patients were of Indian origin. The diagnosis ranged from autoimmune diseases to lymphatic cancer which posed a unique challenge both in the terms of diagnosis and management.

Conclusion

A thorough systematic evaluation along with a multidisciplinary approach is mandatory in the diagnosis of unusual head and neck pathologies.
Provider perceptions of systems-level barriers and facilitators to utilizing family-based treatment approaches in adolescent and young adult opioid use disorder treatment
Authors: Pielech Melissa , Modrowski Crosby , Yeh Jasper , Clark Melissa A. , Marshall Brandon D. L. , Beaudoin Francesca L. , Becker Sara J. , Miranda Robert
Published: March 2024

Background

Amidst increasing opioid-related fatalities in adolescents and young adults (AYA), there is an urgent need to enhance the quality and availability of developmentally appropriate, evidence-based treatments for opioid use disorder (OUD) and improve youth engagement in treatment. Involving families in treatment planning and therapy augments medication-based OUD treatment for AYA by increasing treatment engagement and retention. Yet, uptake of family-involved treatment for OUD remains low. This study examined systems-level barriers and facilitators to integrating families in AYA OUD treatment in Rhode Island.

Methods

An online survey was administered to clinic leaders and direct care providers who work with AYA in programs that provide medication and psychosocial treatments for OUD. The survey assessed attitudes towards and experiences with family-based treatment, barriers and facilitators to family-based treatment utilization, as well as other available treatment services for AYA and family members. Findings were summarized using descriptive statistics.

Results

A total of 104 respondents from 14 distinct treatment programs completed the survey. Most identified as White (72.5%), female (72.7%), and between 25 and 44 years of age (59.4%). Over half (54.1%) of respondents reported no experience with family based treatment and limited current opportunities to involve families. Barriers perceived as most impactful to adopting family-based treatment were related to limited available resources (i.e. for staff training, program expansion) and lack of prioritization of family-based treatment in staff productivity requirements. Barriers perceived as least impactful were respondent beliefs and attitudes about family-based treatment (e.g., perception of the evidence strength and quality of family-based treatment, interest in implementing family-based treatment) as well as leadership support of family-based treatment approaches. Respondents identified several other gaps in availability of comprehensive treatment services, especially for adolescents (e.g. services that increase social recovery capital).

Conclusions

Family-based treatment opportunities for AYA with OUD in Rhode Island are limited. Affordable and accessible training programs are needed to increase provider familiarity and competency with family-based treatment. Implementation of programming to increase family involvement in treatment (i.e. psychoeducational and skills-based groups for family members) rather than adopting a family-based treatment model may be a more feasible step to better meet the needs of AYA with OUD.

Trial registration: not applicable.
Validation of a size exclusion method for concomitant purification and formulation of peptide radiopharmaceuticals
Authors: Martin Sebastian , Wendlinger Lennard , Litvinenko Alexandra , Faizova Radmila , Schottelius Margret
Published: March 2024

Background

Both in clinical routine and in preclinical research, the established standard procedure for the final purification of radiometal-labeled peptide radiopharmaceuticals is cartridge-based reversed-phase (RP) solid phase extraction (SPE). It allows the rapid and quantitative separation of the radiolabeled peptide from hydrophilic impurities and easy integration into automated synthesis procedures. However, product elution from RP cartridges necessitates the use of organic solvents and product recovery is sometimes limited. Thus, an alternative purification method based on commercially available size exclusion cartridges was investigated.

Results

Since most peptide radiopharmaceuticals have a molecular weight > 1 kDa, Sephadex G10 cartridges with a molecular size cut-off of 700 Da were used for the final purification of a broad palette of 68Ga-, 64Cu- and 99mTc-labeled experimental peptide radiotracers as well as the clinically relevant ligand PSMA-617. Results (radiochemical purity (RCP, determined by ITLC), recovery from the solid support) were compared to the respective standard RP-SPE method. Generally, retention of unreacted 68Ga, 64Cu and 99mTc salts on the G10 cartridges was quantitative up to the specified elution volume (1.2 mL) for 68Ga and 99mTc and 99.6% for 64Cu. Even at increased elution volumes of 1.5-2 mL, RCPs of the eluted 68Ga- and 99mTc -radiopeptides were > 99%. For all peptides with a molecular weight ≥ 2 kDa, product recovery from the G10 cartridges was consistently > 85% upon respective adjustment of the elution volume. Product recovery was lowest for [68Ga]Ga-PSMA-617 (67%, 1.2 mL to 84%, 2 mL). The pH of the final product solution was found to be volume-dependent (1.2 mL: pH 6.3; 1.5 mL: pH 5.9; 2 mL: pH 5.5). Notably, the G10 cartridges were reused up to 20 times without compromising performance, and implementation of the method in an automated radiosynthesis procedure was successful.

Conclusions

Overall, size exclusion purification yielded all peptide radiopharmaceuticals in excellent radiochemical purities (> 99%) in saline within 10–12 min. Although product recovery is marginally inferior to classical SPE purifications, this method has the advantage of completely avoiding organic solvents and representing a cost-effective, easy-to-implement purification approach for automated radiotracer synthesis.
The challenge of using patient reported outcome measures in clinical practice: how do we get there?
Authors: Cella David , Nolla Kyle , Peipert John Devin
Published: March 2024

Background

As patient-reported outcome measures (PROMs) become available to clinicians for routine clinical decision-making, many wonder how to define a meaningful change in a patient’s PROM score. Some PROMs have a specific threshold that indicates meaningful change, but since those numbers are based on population averages, they do not necessarily apply to the varying experiences of each individual patient. Rather than viewing this as a weakness of PROMs, it is worth considering how clinicians use other existing measures in clinical decision-making—and whether PROMs can be used similarly.

Body

An informal survey of 43 clinicians reported using measures such as weight, blood pressure, and blood chemistry to inform clinical decision-making. Although clinicians were very consistent with what constituted a meaningful change for some measures (e.g., ECOG performance status), other measures had considerable variability (e.g., weight), often informed by their specialization (for example, differing thresholds for meaningful weight change for adult primary care, pediatrics, and oncology). For interpreting change in measures, they relied on clinical experience (44%), published literature (38%), and established guidelines (35%). In open-response comments, many clarified that the results of any measure had to be taken in the context of each individual patient before making treatment decisions. In short, clinicians already apply individualized clinical judgment when interpreting score changes in existing clinical measures. As clinicians gain familiarity with PROMs, PROMs will likely be utilized in the same way.

Conclusion

Like other clinical measures from weight to blood chemistry, change in a PROM score is but one piece of a patient’s clinical story. Rather than relying on a hard-and-fast number for defining clinically meaningful change in a PROM score, providers should—and many already do—consider the full scope of a patient’s experience as they make treatment decisions.
Hip-specific and generic patient-reported outcome measure scores after primary hip replacement are associated with early revision surgery: a national registry study
Authors: Ackerman Ilana N. , Cashman Kara , Lorimer Michelle , Heath Emma , Harris Ian A.
Published: March 2024

Background

The ability to efficiently identify patients at higher risk of poor outcomes after joint replacement would enable limited resources for post-operative follow-up to be directed to those with the greatest clinical need. This is particularly important as joint replacement rates continue to grow internationally, stretching health system capabilities. Patient-reported outcome measures (PROMs) are routinely administered in many settings and offer an opportunity to detect suboptimal patient outcomes early. This study aimed to determine whether hip-specific and generic PROM scores are associated with early revision hip replacement within six to 24 months after the primary procedure.

Methods

Pre-operative and six-month post-operative PROM scores for patients undergoing primary total hip replacement (THR) were obtained from the Australian Orthopaedic Association National Joint Replacement Registry and Arthroplasty Clinical Outcomes Registry National and linked to revision surgery data. Clinically important improvement was defined using anchor-based thresholds. Associations between PROM scores (hip pain, Oxford Hip Score, HOOS-12, EQ-5D-5L, EQ VAS, patient-perceived change, satisfaction) and revision surgery were evaluated using t-tests, chi-square tests and regression models.

Results

Data were analysed for 21,236 primary THR procedures between 2013 and 2022. Eighty-eight revision procedures were performed at six to 24 months. Patients who were revised had more back pain and worse HOOS-12 scores pre-operatively but between-group differences were small. Worse post-operative PROM scores (hip pain, Oxford, HOOS-12, EQ-5D-5L, EQ VAS) were associated with early revision, after adjusting for age and sex (p < 0.001 for all analyses). Patient dissatisfaction (relative risk (RR) 10.18, 95%CI 6.01–17.25) and patient-perceived worsening (RR 19.62, 95%CI 11.33–33.98) were also associated with a higher likelihood of revision. Patients who did not achieve clinically important improvement in hip pain, function, or quality of life had a higher revision risk (RRs 2.54–5.64), compared with those who did (reference).

Conclusion

Six-month hip-specific and generic PROM scores can identify patients at higher risk of early revision surgery. Our data highlight the utility of routine post-operative PROM assessment for signaling suboptimal surgical outcomes.
Nahua Fasting in a Series of Don'ts: An Interpretation of the Precontact Nezahualiztli Practice
Authors: Madajczak Julia
Published: March 2024

Although the precontact Nahua nezahualiztli ritual received significant coverage in historical sources, the Christian discourse of these sources misinterpreted it as either fasting or penance, inscribing nezahualiztli in the Western idea of the sacred. In order to learn more about the Nahua worldview, this article uses methods derived from philology, cognitive linguistics, and anthropology to reconstruct the meaning that nezahualiztli had for the precontact Nahua. I review numerous mentions of this ritual in the sources and discuss three examples involving nezahualiztli. I conclude that avoiding some hygienic practices, fasting, and abstaining from sex, among other forms of abstinence, allowed humans to assimilate with the deities and dead who inhabited the world beyond. The Nahua observed nezahualiztli whenever they needed to enter a liminal state, such as during funerals, travel, or creative actions. This insight adds to our understanding of the Nahua sacred, particularly the relationship between humans and gods.
The “Indios” of Spain and the Mexican Revolution: Racial Ideologies and the Labor of Internationalist Solidarity
Authors: Aguilar Kevan Antonio
Published: March 2024

This article examines the influence of the Mexican Revolution (1906–40) on Spanish anarchists’ views on racial and class solidarity. Whereas recent transnational studies of the Spanish Civil War (1936–39) have highlighted the conflict's lingering imprint on Latin American politics and society, this essay explores why Spanish anarchists interpreted the Mexican Revolution as an insurrection led by Mexico's Indigenous communities. It argues that such readings of the conflict, most of which were advanced by non-Indigenous revolutionaries, both challenged and reinforced racialized notions of social and political upheaval. This article therefore demonstrates how these views challenged orthodox interpretations of social revolution while exposing the obstacles to building internationalist solidarity among laboring classes in postimperial and postcolonial societies.
A Rad50-null mutation in mouse germ cells causes reduced DSB formation, abnormal DSB end resection and complete loss of germ cells
Authors: Liu Yuefang , Lin Zhen , Yan Junyi , Zhang Xi , Tong Ming-Han
Published: March 2024

The conserved MRE11-RAD50-NBS1/Xrs2 complex is crucial for DNA break metabolism and genome maintenance. Although hypomorphic Rad50 mutation mice showed normal meiosis, both null and hypomorphic rad50 mutation yeast displayed impaired meiosis recombination. However, the in vivo function of Rad50 in mammalian germ cells, particularly its in vivo role in the resection of meiotic double strand break (DSB) ends at the molecular level remains elusive. Here, we have established germ cell-specific Rad50 knockout mouse models to determine the role of Rad50 in mitosis and meiosis of mammalian germ cells. We find that Rad50-deficient spermatocytes exhibit defective meiotic recombination and abnormal synapsis. Mechanistically, using END-seq, we demonstrate reduced DSB formation and abnormal DSB end resection occurs in mutant spermatocytes. We further identify that deletion of Rad50 in gonocytes leads to complete loss of spermatogonial stem cells due to genotoxic stress. Taken together, our results reveal the essential role of Rad50 in mammalian germ cell meiosis and mitosis, and provide in vivo views of RAD50 function in meiotic DSB formation and end resection at the molecular level.
Decreased hippocampal microglial cell activation by methanolic extract from the leaves of Mallotus oppositifolius (Geiseler) Müll. Arg contributes to its antidepressant-like effect
Authors: Kukuia Kennedy Kwami Edem , Takyi Ferka Yaw , Dugbartey George Johnson , Amoateng Patrick , Kudzi William , Amponsah Seth Kwabena , Koomson Awo Efua , Appiah Frimpong , Adi-Dako Ofosua , Ameyaw Elvis Ofori , Adutwum-Ofosu Kevin Kofi
Published: March 2024

Background Natural remedies with neuroprotective effect are useful in neuroinflammation-associated depression. Although Mallotus oppositifolius extract (MOE) has previously demonstrated antidepressant and anti-inflammatory properties, its neuroprotective effect remains unknown. Thus, the study evaluated the effect of MOE on lipopolysaccharide (LPS)-induced neuroinflammation-associated depression in mice. Methods Antidepressant-like effect of MOE (10 – 100 mg/kg), fluoxetine (20 mg/kg) and minocycline (50 mg/kg) was established in naïve Institute of Cancer Research (ICR) mice using the forced swim (FST), tail suspension (TST) and open-space swim (OSST) tests. In a separate experiment, FST and TST were used to assess the effect of an 11-day pre-treatment with MOE (10 – 100 mg/kg) or minocycline (50 mg/kg) on LPS (1 mg/kg) neuroinflammation at 6 and 24 hours post LPS. Following these tests, mice were sacrificed and their hippocampi isolated to evaluate their resting and activated microglial cells using Golgi-Cox staining technique. Open-field test was used to assess locomotor activity. Results MOE, fluoxetine and minocycline significantly reduced immobility in FST, TST and OSST compared to vehicle (p < 0.05), confirming their antidepressant-like effect. Interestingly, MOE’s antidepressant-like effect was faster than fluoxetine and minocycline. Conversely, LPS treatment increased immobility behavior at 6 and 24 hours, suggestive of neuroinflammation-induced depression. Compared to vehicle group, pre-treatment with MOE and minocycline ameliorated LPS-induced hippocampal microglial activation and reversed increased immobility behavior without affecting locomotor activity (p < 0.05). Resting microglial cell count was significantly increased by MOE pre-treatment in the OSST-challenged mice compared to vehicle group (p < 0.01). Similarly, MOE pre-treatment reversed LPS-induced reduction in resting microglial count, and restored resting microglial count to normal levels compared to LPS naive vehicle group. Conclusions Collectively, the results suggest that MOE exerts neuroprotective effect against LPS-induced neuroinflammation by decreasing the activation of microglia and increasing resting microglial count. This contributes to its antidepressant-like effect.
Human judgement forecasting of COVID-19 in the UK
Authors: Bosse Nikos I. , Abbott Sam , Bracher Johannes , van Leeuwen Edwin , Cori Anne , Funk Sebastian
Published: March 2024

Background In the past, two studies found ensembles of human judgement forecasts of COVID-19 to show predictive performance comparable to ensembles of computational models, at least when predicting case incidences. We present a follow-up to a study conducted in Germany and Poland and investigate a novel joint approach to combine human judgement and epidemiological modelling. Methods From May 24th to August 16th 2021, we elicited weekly one to four week ahead forecasts of cases and deaths from COVID-19 in the UK from a crowd of human forecasters. A median ensemble of all forecasts was submitted to the European Forecast Hub. Participants could use two distinct interfaces: in one, forecasters submitted a predictive distribution directly, in the other forecasters instead submitted a forecast of the effective reproduction numberRt. This was then used to forecast cases and deaths using simulation methods from the EpiNow2 R package. Forecasts were scored using the weighted interval score on the original forecasts, as well as after applying the natural logarithm to both forecasts and observations. Results The ensemble of human forecasters overall performed comparably to the official European Forecast Hub ensemble on both cases and deaths, although results were sensitive to changes in details of the evaluation.Rtforecasts performed comparably to direct forecasts on cases, but worse on deaths. Self-identified “experts” tended to be better calibrated than “non-experts” for cases, but not for deaths. Conclusions Human judgement forecasts and computational models can produce forecasts of similar quality for infectious disease such as COVID-19. The results of forecast evaluations can change depending on what metrics are chosen and judgement on what does or doesn't constitute a "good" forecast is dependent on the forecast consumer. Combinations of human and computational forecasts hold potential but present real-world challenges that need to be solved.
Bioremediation of toxic metals and Limnocharis flava (L.) Buchenau growth in acidic contaminated soil supported by microbial inoculants
Authors: Nguyen Thilam , Song Shaoxian , Dung Bui Thi Ngoc , Ahmed Samreen Riaz , Lahori Altaf Hussain
Published: March 2024

An in situ pot experiment was carried out in a net house to study the combined effect of a mixture of microbial inoculants at different levels of 0, 1, 1.5, 2, 2.5, and 3 g/kg in dry soil with Limnocharis flava (L.) Buchenau plants grown on agricultural land contaminated with lead (Pb) and cadmium (Cd). The results showed that plant growth, fresh inflorescence yields and accumulation of Pb and Cd in L. flava plant parts gradually increased with increasing levels of the applied microbial inoculants in the contaminated soil. The highest total content of Pb and Cd was determined in roots (6.63–32.46 and 0.12–0.72 mg/kg dw), followed by stems and leaves (1.20–3.08 and 0.04–0.09 mg/kg dw) and inflorescence parts (0.012–0.120 and 0.011–0.065 mg/kg fw). The application of microbial inoculants in the range of 2–2.5 g/kg dry soil stimulated the growth and fresh inflorescence yields of L. flava, increased the accumulation of Pb and Cd in inedible parts, ensuring safety for edible parts of L. flava plants in accordance with QCVN8-2:2011/BYT and FAO/WHO regulations. The results of the present work indicate that the flexibility of Pb and Cd can be increased when soil is mixed with microbial inoculants. Long term ex situ experiments are needed to investigate the impact of microbial inoculants mixed with biochar, minerals and nanomaterial for phytomanagement of soil contaminated with multiple metals.
Avifaunal Diversity in Managed Urban Ecosystem: A Case Study of Banaras Hindu University, Varanasi
Authors: Singh Rinku , Tiwari Amit Kumar , Kumar Sudhanshu , Singh Gopal Shankar
Published: March 2024

University campuses are becoming important places for conducting a large number of studies on plant and animal taxa including avian diversity. However, a systematic study on the avian diversity in the Banaras Hindu University (BHU) campus (Asia’s largest residential university campus) of Varanasi is still lacking. The present study deals with the species abundance, diversity and species richness of avian communities in the BHU campus. We conducted a bird survey in the BHU campus between 2019 and 2020. Employing line-transect method, a total of 141 bird species under 62 families were recorded from the study area. A rich diversity of species recorded indicates the importance of the university campuses in urbanized region to serve as a critical habitat for birds. To conserve this rich bird diversity of the campus, we suggest sustainable management of habitats through restoration of degraded habitats, reduction in habitat destruction, conservation awareness programmes and increased research on assessment of diversity.
Enhancing Customer–Supplier Coordination Through Customer-Managed Inventory
Authors: Chen Shi , Cohen Morris A. , Lee Hau
Published: March 2024

In recent years, there has been an increasing trend in supply chains to employ a “control tower” approach to improve supply chain performance. One such strategy is customer-managed inventory (CMI) in which the customer (the downstream party) controls the inventory of the supplier (the upstream party). However, the optimal design of the inventory control policy and the required incentive structure for CMI has not been fully explored in the related literature. In this paper, we develop a two-echelon model consisting of a supplier and a customer that captures the interaction between both decision makers. Analysis of this model indicates that achieving the potential benefits of CMI requires suitable incentive mechanisms to be put in place. The two-echelon inventory system model, however, does not give closed-form solutions, which are required to generate an optimal solution to the inventory control and incentive problem. To address this challenge, we propose an approximate model, which decouples the two-echelon model into two newsvendor-type models with each party operating a single-echelon system. This approximate model requires the introduction of additional cost parameters so that the decoupled model captures the cost implications of supplier shortages in the original two-echelon model. By developing appropriate values for these cost parameters, the approximate model yields near optimal results. Analysis of the solution reveals important operational factors that determine which environments are conducive for CMI and conditions for Pareto improvement of all stakeholders.

This paper was accepted by Jayashankar Swaminathan, operations management.

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2021.03658 .
Technical Note—An Unexpected Stochastic Dominance: Pareto Distributions, Dependence, and Diversification
Authors: Chen Yuyu , Embrechts Paul , Wang Ruodu
Published: March 2024

Diversification is generally regarded as an efficient tool to reduce portfolio risks. In “An unexpected stochastic dominance: Pareto distributions, dependence, and diversification,” Chen, Embrechts, and Wang showed that the weighted average of independent and identically distributed (i.i.d.) Pareto random variables with infinite mean is larger than one such random variable in the sense of first-order stochastic dominance, and thus diversification is, surprisingly, worse than no diversification. The relation implies superadditivity of value-at-risk, a regulatory risk measure used in the finance and insurance sectors. The obtained relation also holds under some form of negative dependence.
You Can Check Out Any Time You Like, but Can You Ever Leave? A Theory of Firm Value Capture from Alumni
Authors: Fulmer Ingrid Smithey , Call Matthew L. , Conlon Donald E. , Klotz Anthony C.
Published: March 2024

In modern organizations, key sources of competitive advantage are embedded in employees. Management theory has traditionally viewed employee exit as the end of firms’ relationships with employees and, consequently, the end of access to human capital and other resources embedded in departing individuals. However, recent research suggests that firms can benefit from the continuation of relationships with alumni employees. We argue that how organizations create and maintain connections to alumni is critical, as it shapes the nature of potentially valuable organization-level alumni resources. We develop a theory of firm value capture from alumni that explains how firms’ norms and policies before, during, and after employee exit affect firms’ alumni relations climate—a shared perception among a firm’s current and former employees that the firm values alumni. We further theorize that the alumni relations climate will lead to creation of firm-level alumni resources, with the configuration of these resources shaped by alumni identification. That is, the extent to which firms’ alumni identify with the firm versus with members of the firm’s remaining workforce (or balanced between the two) will have implications for the configuration of alumni resources that are potentially accessible to the firm. Our theory describes how these different alumni resource configurations come with inherent benefits and costs when it comes to the value that firms are able to capture from their alumni resources. We illustrate the value of this theoretical perspective by identifying meaningful practical implications and avenues for future research.
Linear Lexicographic Optimization and Preferential Bidding System
Authors: Tellache Nour ElHouda , Meunier Frédéric , Parmentier Axel
Published: March 2024

Some airlines use the preferential bidding system to construct the schedules of their pilots. In this system, the pilots bid on the different activities and the schedules that lexicographically maximize the scores of the pilots according to their seniority are selected. A sequential approach to solve this maximization problem is natural: The problem is first solved with the bids of the most senior pilot, and then it is solved with those of the second most senior without decreasing the score of the most senior, and so on. The literature admits that the structure of the problem somehow imposes such an approach. The problem can be modeled as an integer linear lexicographic program. We propose a new efficient method, which relies on column generation for solving its continuous relaxation and returns proven optimality gaps. To design this column generation, we prove that bounded linear lexicographic programs admit “primal-dual” feasible bases, and we show how to compute such bases efficiently. Another contribution on which our method relies is the extension of standard tools for resource-constrained longest path problems to their lexicographic versions. This is useful in our context because the generation of new columns is modeled as a lexicographic resource-constrained longest path problem. Numerical experiments show that this new method is already able to solve to proven optimality industrial instances provided by Air France, with up to 150 pilots. By adding a last ingredient in the resolution of the longest path problems, which exploits the specificity of the preferential bidding system, the method achieves for these instances computational times that are compatible with operational constraints.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2022.0372 .
On the genus Parvocaecus Coiffait of Turkey: Three new species from Anatolia, an identification key and annotated catalogue of the genus (Coleoptera: Carabidae: Trechinae: Anillini)
Authors: LOHAJ ROMAN , ANLAŞ SINAN
Published: March 2024

Three new species of the genus Parvocaecus Coiffait, 1956 from Turkey are described, illustrated and compared with the related species: Parvocaecus smatanai sp. nov. (Type locality Konya, Beyşehir, Çamlık), Parvocaecus bozdagensis sp. nov. (Type locality Manisa, Alaşehir, Bozdağlar) and Parvocaecus orgeli sp. nov. (Type locality Kırıkkale, Balişeyh, Uzunlar-Gazibeyli Road). These newly described species were individually collected, either under deeply inserted stones or using subterranean pitfall traps placed in the mesovoid shallow substratum (MSS). An identification key, distribution check-list, and map of the genus are also provided.
Yükseköğretim İngilizce Hazırlık Öğretim Programında Program Esnekliğinin İncelenmesi
Authors: Oruç Eylem , Aydemir Sevilay
Published: March 2024

Bu araştırmada bir yükseköğretim kurumunda hazırlık yabancı dil öğretim programının hazırlanması ve öğretim etkinliklerinin uygulanması aşamalarında öğretim elemanlarının deneyimlerine ilişkin görüşleri incelenmiş ve program esnekliğini nasıl sağladıkları belirlenmeye çalışılmıştır. Literatürdeki esnek öğretim programı ve esnek öğrenme kavramlarının tanımlarından ve açıklamalarından yararlanılarak öğretim elemanlarının deneyimleri, onların görüşleri doğrultusunda yorumlanmaya çalışılmıştır. Araştırma sorularına yanıt aramak için nitel araştırma türlerinden biri olan olgu bilim deseninden yararlanılmıştır. Araştırmanın katılımcıları ölçüt örnekleme yöntemi ile belirlenen yedi öğretim elemanından oluşmaktadır. Araştırma verileri odak grup görüşmesi yoluyla toplanmıştır. Araştırmacılar tarafından hazırlanan yapılandırılmış görüşme formuyla elde edilen verilerin analizinde içerik analizi yöntemi kullanılmıştır. Araştırma sonuçları genel olarak değerlendirildiğinde; araştırmaya katılan öğretim elemanlarının yabancı dil programının hazırlanması sürecindeki kararlarda öğrenci katılımını sağladıkları, gerektiğinde öğrenci ilgi ve ihtiyaçlarına göre öğrenme etkinliklerinde değişiklikler yaptıkları belirlenmiştir. Öğretim elemanlarının öğrenci katılımını destekleyici öğrenme ortamları sunmaları, öğrenme sürecini ders dışı etkinliklerle zenginleştirmeleri onların esnek program anlayışına sahip olduklarını göstermektedir. Diğer yandan öğretim elemanlarının iş yükü ve öğrencilerin ders dışı etkinliklere katılma konusundaki isteksizliği yabancı dil öğretiminde bazı etkinliklerin beklenen düzeyde uygulanamamasına neden olmaktadır. Sonuç olarak, öğretim elemanlarının görüşlerine göre yabancı dil öğretim programında öğrencilerin ilgi, ihtiyaç ve beklentilerini karşılamak için yapılan esnek program uygulamalarının öğrenci katılımını, motivasyonunu, özgüvenini ve öğrenme sorumluluğunu arttırmada olumlu etkileri bulunduğu belirlenmiştir.
Examination of the Antioxidant and Anti-inflammatory Effects of Extracts from the Bark of Bangladesh Medicinal Plants
Authors: Lee Joo Won , Kim Mi-Bo , Jeong Seungjin , Lee Hyeju , Baek Su Hyeon , Salah Uddin Md. , Lee Sang Woo , Lee Sang Gil
Published: March 2024

Bangladeshi medicinal plants (BMP) have a history of traditional use in treating chronic inflammatory diseases, but a BMP bark’s antioxidant and anti-inflammatory effects remain largely unexplored. This study assessed methanolic extracts’ antioxidant and anti-inflammatory properties from the bark of 15 medicinal plant species native to Bangladesh. The methanol extracts of BMP bark were evaluated for their total antioxidant activity and ability to counteract inflammation induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Among the 15 bark extracts from BMP, Albizia odoratissima (A. odoratissima), Engelhardia spicata (E. spicata), and Shorea robusta (S. robusta) showed the highest total phenolic contents and total antioxidant capacity by effectively scavenging free radicals. In particular, these three bark extracts significantly reduced the mRNA expression of LPS-induced inflammatory cytokines and enzymes inducible by inflammation in macrophages. Also, the mRNA expression of NADPH oxidase 2 was significantly suppressed by the three bark extracts in LPS-induced RAW 264.7 macrophages. These results suggest that out of the 15 bark extracts obtained from medicinal plants in Bangladesh, the extracts from A. odoratissima, E. spicata, and S. robusta exhibit substantial total antioxidant capacity by efficiently scavenging free radicals and also inhibit LPS-induced inflammation in macrophages.
Alleviation of Hangover Effects by DA-5521: A Randomized, Double-blind, Placebo-Controlled, Crossover Trial
Authors: Lee Sulhee , Choi Sang-Pil , Park Eun-Ock , Jung Su-Jin , Chae Soo-Wan , Park Young-Seo
Published: March 2024

Animal experiments have demonstrated the effectiveness of fermented rice germ and soybean extracts in lowering blood alcohol concentration. A compound primarily derived from fermented soybean extract constitutes the principal component of DA-5521, an experimental dietary substance examined in this study. We investigated the possible hangover-alleviating effects of DA-5521 in individuals aged 19 to 50 who had previously experienced hangovers. Moreover, we enrolled 22 participants who met the eligibility criteria and conducted a double-blind, randomized, placebo-controlled crossover trial. Six hours after alcohol consumption, the test group exhibited a statistically significant reduction in blood acetaldehyde concentration compared with the placebo group. Further, our results displayed significantly lower levels in the DA- 5521 group at 0.50 and 0.75 h post-ingestion and substantially lower peak breath alcohol concentration compared to the placebo group. These findings confirm that consumption of DA-5521 can significantly ameliorate hangover symptoms by diminishing blood acetaldehyde concentration and reduce breath alcohol concentration.
Physicochemical Property of Protein-Fortified Rice Flour Using Bacillus subtilis-Fermented Faba Bean Protein Concentrate and Chickpea Flour
Authors: Park Su-Won , Lee Jungae , Kim Hyun-Seok
Published: March 2024

This study investigated the physicochemical properties of protein-fortified rice flour by mixing rice flour (RF) with untreated and fermented plant proteins. Fermented faba bean protein concentrate (FMFP) and chickpea flour (FMCF) were prepared by solid-state fermentation of faba bean protein concentrate (UTFP) and chickpea flour (UTCF) using Bacillus subtilis. FMFP and FMCF exhibited higher crude protein, reducing sugar and starch contents more than their counterparts. The increased rate of essential and branched-chain amino acids in FMFP and FMCF exceeded that of crude protein. Adding plant proteins to RF decreased swelling power (SP) and increased solubility in RF-UTFP and RF-FMFP mixtures, while SP and solubility increased in RF-UTCF and RF-FMCF mixtures. All RF-plant protein mixtures showed higher gelatinization temperature and lower gelatinization enthalpy than RF. Thermal gelation was found in all RF-plant protein mixtures, but the RF-FMCF mixture may form weak and unstable gel structures. The increase in pasting viscosity was minimal for the RF-UTFP and RF-FMFP mixtures but more pronounced for the RF-UTCF and RF-FMCF mixtures. Overall, FMFP may be a potential protein source to supplement the protein deficiency in RF with minimal changes in RF-based foods’ rheological and textural properties.
Risky event classification leveraging transfer learning for very limited datasets in optical networks
Authors: Abdelli Khouloud , Lonardi Matteo , Gripp Jurgen , Olsson Samuel , Boitier Fabien , Layec Patricia
Published: March 2024

Monitoring the state of polarization (SOP) is crucial for tracking vibrations or disturbances in the vicinity of optical fibers, such as precursors to fiber cuts. While SOP data are valuable for machine learning (ML) models in identifying vibrations, acquiring a sufficient amount of data presents a significant challenge. To overcome this hurdle, we introduce an innovative transfer learning framework designed for the identification of vibrations (events) when confronted with limited SOP data. Our methodology leverages the pre-trained convolutional neural network MobileNet as a feature extractor, incorporating the encoding of time series SOP measurements into images for MobileNet input. We explore different time series encoding techniques, including the Gramian Angular Difference Field (GADF) and the Gramian Angular Summation Field (GASF). Different architectures for building our transfer learning framework based on MobileNet are investigated. Validation of our proposed approaches is conducted using experimental data that simulates movements indicative of fiber break precursors. The experimental results clearly demonstrate the superior performance of our approaches compared to other ML algorithms, especially in scenarios with limited data. Furthermore, our framework surpasses pre-trained CNN models in terms of predictive power, affirming its effectiveness in enhancing the accuracy of vibration identification in the presence of constrained SOP data.
Ethical frameworks should be applied to computational modelling of infectious disease interventions
Authors: Zachreson Cameron , Savulescu Julian , Shearer Freya M. , Plank Michael J. , Coghlan Simon , Miller Joel C. , Ainslie Kylie E. C. , Geard Nicholas
Published: March 2024

This perspective is part of an international effort to improve epidemiological models with the goal of reducing the unintended consequences of infectious disease interventions. The scenarios in which models are applied often involve difficult trade-offs that are well recognised in public health ethics. Unless these trade-offs are explicitly accounted for, models risk overlooking contested ethical choices and values, leading to an increased risk of unintended consequences. We argue that such risks could be reduced if modellers were more aware of ethical frameworks and had the capacity to explicitly account for the relevant values in their models. We propose that public health ethics can provide a conceptual foundation for developing this capacity. After reviewing relevant concepts in public health and clinical ethics, we discuss examples from the COVID-19 pandemic to illustrate the current separation between public health ethics and infectious disease modelling. We conclude by describing practical steps to build the capacity for ethically aware modelling. Developing this capacity constitutes a critical step towards ethical practice in computational modelling of public health interventions, which will require collaboration with experts on public health ethics, decision support, behavioural interventions, and social determinants of health, as well as direct consultation with communities and policy makers.
Harnessing Schistosoma-associated metabolite changes in the human host to identify biomarkers of infection and morbidity: Where are we and what should we do next?
Authors: Kameni Mireille , Musaigwa Fungai , Kamguia Leonel Meyo , Kamdem Severin Donald , Mbanya Gladice , Lamberton Poppy H. L. , Komguep Nono Justin
Published: March 2024

Schistosomiasis is the second most widespread parasitic disease affecting humans. A key component of today’s infection control measures is the diagnosis and monitoring of infection, informing individual- and community-level treatment. However, newly acquired infections and/or low parasite burden are still difficult to diagnose reliably. Furthermore, even though the pathological consequence of schistosome egg sequestration in host tissues is well described, the evidence linking egg burden to morbidity is increasingly challenged, making it inadequate for pathology monitoring. In the last decades, omics-based instruments and methods have been developed, adjusted, and applied in parasitic research. In particular, the profiling of the most reliable determinants of phenotypes, metabolites by metabolomics, emerged as a powerful boost in the understanding of basic interactions within the human host during infection. As such, the fine detection of host metabolites produced upon exposure to parasites such as Schistosoma spp. and the ensuing progression of the disease are believed to enable the identification of Schistosoma spp. potential biomarkers of infection and associated pathology. However, attempts to provide such a comprehensive understanding of the alterations of the human metabolome during schistosomiasis are rare, limited in their design when performed, and mostly inconclusive. In this review, we aimed to briefly summarize the most robust advances in knowledge on the changes in host metabolic profile during Schistosoma infections and provide recommendations for approaches to optimize the identification of metabolomic signatures of human schistosomiasis.