bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance investigation of a V-trough concentrating agrivoltaic system based on spectral splitting
Authors: Liang Xiaomin , Hu Yue , Yao Yucheng , Lv Hui
Published: March 2024

In order to improve the comprehensive utilization efficiency of solar energy, a V-trough concentrating and splitting agrivoltaic hybrid system (VCSPVA system) is proposed in this paper, which transmits the red and blue spectral bands to crop field for photosynthesis conversion and concentrates the other bands to the solar panels for photoelectric conversion. Then, the power generation is completed with sustaining the crop growth, while the overall utilization efficiency of solar energy is improved significantly. The influence of key parameters is studied in detail. Results show that by adjusting trough angles, more reflected radiation can be received by the solar panels, minimizing the energy loss of the system. Through mathematical model establishment, the energy, economic and carbon emission evaluations of the proposed system are carried out. Consequently, the VCSPVA system has the highest annual efficiency of 16.96%, which is 39.15% and 45.93% higher than that of the traditional agrivoltaic system and photovoltaic-only system, respectively. Meanwhile, the net present value and carbon emission mitigation are $758680.99 and 0.25 t·m−2·a−1, respectively, which demonstrates a competitive option for dual land use and a significant role in reducing greenhouse gas emissions.
A flexible high-throughput cultivation protocol to assess the response of individuals’ gut microbiota to diet-, drug-, and host-related factors
Authors: Zünd Janina N , Plüss Serafina , Mujezinovic Denisa , Menzi Carmen , von Bieberstein Philipp R , de Wouters Tomas , Lacroix Christophe , Leventhal Gabriel E , Pugin Benoit
Published: March 2024

The anaerobic cultivation of fecal microbiota is a promising approach to investigating how gut microbial communities respond to specific intestinal conditions and perturbations. Here, we describe a flexible protocol using 96-deepwell plates to cultivate stool-derived gut microbiota. Our protocol aims to address gaps in high-throughput culturing in an anaerobic chamber. We characterized the influence of the gas phase on the medium chemistry and microbial physiology and introduced a modular medium preparation process to enable the testing of several conditions simultaneously. Furthermore, we identified a medium formulation that maximized the compositional similarity of ex vivo cultures and donor microbiota while limiting the bloom of Enterobacteriaceae. Lastly, we validated the protocol by demonstrating that cultivated fecal microbiota responded similarly to dietary fibers (resistant dextrin, soluble starch) and drugs (ciprofloxacin, 5-fluorouracil) as reported in vivo. This high-throughput cultivation protocol has the potential to facilitate culture-dependent studies, accelerate the discovery of gut microbiota-diet-drug-host interactions, and pave the way to personalized microbiota-centered interventions.
Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients
Authors: Wenker Suzanne A M , Alabdulkarim Najla , Readman John B , Slob Elise M A , Satta Giovanni , Ali Shanom , Gadher Nishma , Shulman Rob , Standing Joseph F
Published: March 2024

Background

It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%–100% fT>1–4×MIC). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes.

Objectives

The first aim of this study was to define the optimal PK/PD index of piperacillin/tazobactam with a hollow-fibre infection model (HFIM). The second aim was to predict whether these PK/PD targets are currently achieved in critically ill patients through PK/PD model simulation.

Patients and methods

A dose-fractionation study comprising 21 HFIM experiments was performed against a range of Gram-negative bacterial pathogens, doses and infusion times. Clinical data and dose histories from a case series of nine patients with a known bacterial infection treated with piperacillin/tazobactam in the ICU were collected. The PK/PD index and predicted plasma concentrations and therefore target attainment of the patients were simulated using R version 4.2.1.

Results

fT >MIC was found to be the best-fitting PK/PD index for piperacillin/tazobactam. Bactericidal activity with 2 log10 cfu reduction was associated with 77% fT>MIC. Piperacillin/tazobactam therapy was defined as clinically ‘ineffective’ in ∼78% (7/9) patients. Around seventy-one percent (5/7) of these patients had a probability of >10% that 2  log10 cfu reduction was not attained.

Conclusions

Our dose-fractionation study indicates an optimal PK/PD target in piperacillin/tazobactam therapies should be 77% fT>MIC for 2 log10 kill. Doses to achieve this target should be considered when treating patients in ICU.
Molecular epidemiological and antimicrobial-resistant mechanisms analysis of prolonged Neisseria gonorrhoeae collection between 1971 and 2005 in Japan
Authors: Kagawa Narito , Aoki Kotaro , Komori Kohji , Ishii Yoshikazu , Shimuta Ken , Ohnishi Makoto , Tateda Kazuhiro
Published: March 2024

Objectives

As antimicrobial-resistant (AMR) Neisseria gonorrhoeae strains have emerged, humans have adjusted the antimicrobials used to treat infections. We identified shifts in the N. gonorrhoeae population and the determinants of AMR strains isolated during the recurring emergence of resistant strains and changes in antimicrobial therapies.

Methods

We examined 243 N. gonorrhoeae strains corrected at the Kanagawa Prefectural Institute of Public Health, Kanagawa, Japan, these isolated in 1971–2005. We performed multilocus sequence typing and AMR determinants (penA, mtrR, porB, ponA, 23S rRNA, gyrA and parC) mainly using high-throughput genotyping methods together with draft whole-genome sequencing on the MiSeq (Illumina) platform.

Results

All 243 strains were divided into 83 STs. ST1901 (n = 17) was predominant and first identified after 2001. Forty-two STs were isolated in the 1970s, 34 in the 1980s, 22 in the 1990s and 13 in the 2000s, indicating a decline in ST diversity over these decades. Among the 29 strains isolated after 2001, 28 were highly resistant to ciprofloxacin (MIC ≥ 8 mg/L) with two or more amino-acid substitutions in quinolone-resistance-determining regions. Seven strains belonging to ST7363 (n = 3), ST1596 (n = 3) and ST1901 (n = 1) were not susceptible to cefixime, and six strains carried penA alleles with mosaic-like penicillin-binding protein 2 (PBP2; penA 10.001 and 10.016) or PBP2 substitutions A501V and A517G.

Conclusions

We observed a significant reduction in the diversity of N. gonorrhoeae over 35 years in Japan. Since 2001, ST1901, which is resistant to ciprofloxacin, has superseded previous strains, becoming the predominant ST population.
A many-objective evolutionary algorithm based on learning assessment and mapping guidance of historical superior information
Authors: Xiong Jinlian , Liu Gang , Gao Zhigang , Zhou Chong , Hu Peng , Bao Qian
Published: March 2024

Multi-objective optimization algorithms have shown effectiveness on problems with two or three objectives. As the number of objectives increases, the proportion of non-dominated solutions increases rapidly, resulting in insufficient selection pressure. Nevertheless, insufficient selection pressure usually leads to the loss of convergence, too intense selection pressure often results in a lack of diversity. Hence, balancing the convergence and diversity remains a challenging problem in many-objective optimization problems. To remedy this issue, a many-objective evolutionary algorithm based on learning assessment and mapping guidance of historical superior information, referred to here as MaOEA-LAMG, is presented. In the proposed algorithm, an effective learning assessment strategy according to historical superior information based on an elite archive updated by indicator ${I}_{\varepsilon + }$ is proposed, which can estimate the shape of the Pareto front and lay the foundation for subsequent fitness and acute angle-based similarity calculations. From this foundation, to balance the convergence and diversity dynamically, a mapping guidance strategy based on the historical superior information is designed, which contains clustering, associating, and proportional selection. The performance of the proposed algorithm is validated and compared with 10 state-of-the-art algorithms on 24 test instances with various Pareto fronts and real-world water resource planning problem. The empirical studies substantiate the efficacy of the results with competitive performance.
State Church and Religious Equality: A Comparative Study of Competing Logics during the Process of Changing Relations between State and Church in Sweden and Norway
Authors: Nylenna Helge K , Lundgren Linnea
Published: March 2024

In recent decades, the religious landscape in the Nordic countries has changed. Transforming from traditional homogeneous Evangelical-Lutheran societies into more religiously and culturally diverse, there have been reforms creating new relationships between the states and the traditional state churches. Taking a comparative approach, this article analyzes how institutional logics guided the church and state reforms in Norway and Sweden. Analyzing governmental documents through the theoretical lens of institutional logics, the article makes a distinction between the logic of state church and the logic of religious equality. The article shows how the former acts as a foundational logic within policymaking even though there has been a movement towards more religious equality in legislation. Though there are differences in how Norway and Sweden facilitate their arrangements for support to faith communities, the ideas informing the arrangements are similar. We point towards an increased discrepancy behind the ideas informing policymaking and the practical implications of those policies.
Potential role of cannabis in ameliorating observed racialized disparities in cancer pain management
Authors: Gibson Laurel P , Ferrer Rebecca A , Meghani Salimah H , Acevedo Amanda M
Published: March 2024

Cancer-related pain affects a large proportion of all patients with cancer yet remains inadequately managed, particularly among patients from certain racialized backgrounds. Recently, there has been increased research and clinical interest in the use of medical cannabis for cancer pain management, including its potential to ameliorate race-based disparities in cancer pain control. Although medical cannabis is not currently a US Food and Drug Administration–approved treatment option for cancer-related pain, many oncologists discuss and recommend its use with their patients, underscoring the need for researchers and clinicians to proactively identify barriers to cannabis for cancer pain management that may disproportionately affect patients from certain racial groups. In this commentary, we highlight challenges that patients from racialized backgrounds may face when incorporating cannabis into their palliative care regimens and discuss opportunities for researchers and clinicians to address these challenges should medical cannabis become a recommended treatment option for cancer pain management. In particular, we identify challenges at the structural (eg, lack of insurance coverage), clinician (eg, racialized stereotypes regarding addiction and pain), and individual (eg, internalized stigma) levels and emphasize the importance of multilevel approaches in combating these challenges as the evidence base regarding medical cannabis and its potential harms and therapeutic benefits continues to accumulate.
Trust at Risk: The Effect of Proximity to Cyberattacks
Authors: Gomez Miguel Alberto , Shandler Ryan
Published: March 2024

Proximity is a core feature of theories of political violence, with the effects of attacks rippling outward so that geographically proximate individuals experience more severe effects than those more distant. However, this model of proximity and exposure is unlikely to recur for cyberattacks. The incorporeality of cyber incidents and the absence of a physical epicenter constrain the mechanism coupling physical distance with harm. To empirically test the relationship between proximity and cyberattacks, we conducted a field study involving 707 German respondents following a ransomware attack in Düsseldorf. We find that the classical “ripple effect” is reversed, with political trust highest among people closer to the attack and lowest among those geographically distant. We postulate that in the absence of firsthand exposure to its effects, geographically distant individuals employ abstract conceptions of the consequences of cyber incidents that do not align with actual events. Consequently, distance does not confer security, and it can even amplify the adverse effects of exposure. This finding highlights the need for governments to actively work to assuage public fears following cyberattacks.
A new test of gravity – I. Introduction to the method
Authors: Armijo Joaquin , Baugh Carlton M , Norberg Peder , Padilla Nelson D
Published: March 2024

We introduce a new scheme based on the marked correlation function to probe gravity using the large-scale structure of the Universe. We illustrate our approach by applying it to simulations of the metric-variation f(R) modified gravity theory and general relativity (GR). The modifications to the equations in f(R) gravity lead to changes in the environment of large-scale structures that could, in principle, be used to distinguish this model from GR. Applying the Monte Carlo Markov Chain algorithm, we use the observed number density and two-point clustering to fix the halo occupation distribution (HOD) model parameters and build mock galaxy catalogues from both simulations. To generate a mark for galaxies when computing the marked correlation function we estimate the local density using a Voronoi tessellation. Our approach allows us to isolate the contribution to the uncertainty in the predicted marked correlation function that arises from the range of viable HOD model parameters, in addition to the sample variance error for a single set of HOD parameters. This is critical for assessing the discriminatory power of the method. In a companion paper, we apply our new scheme to a current large-scale structure survey.
Tex46 knockout male mice are sterile secondary to sperm head malformations and failure to penetrate through the zona pellucida
Authors: Fujihara Yoshitaka , Miyata Haruhiko , Abbasi Ferheen , Larasati Tamara , Nozawa Kaori , Yu Zhifeng , Ikawa Masahito , Matzuk Martin M
Published: March 2024

Each year, infertility affects 15% of couples worldwide, with 50% of cases attributed to men. It is assumed that sperm head shape is important for sperm-zona pellucida (ZP) penetration but research has yet to elucidate why. We generated testis expressed 46 (Tex46) knockout mice to investigate the essential roles of TEX46 in mammalian reproduction. We used RT-PCR to demonstrate that Tex46 was expressed exclusively in the male reproductive tract in mice and humans. We created Tex46−/− mice using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system and analyzed their fertility. Tex46 null spermatozoa underwent further evaluation using computer-assisted sperm analysis, light microscopy, and ultrastructural microscopy. We used immunoblot analysis to elucidate relationships between TEX46 and other acrosome biogenesis-related proteins. Mouse and human TEX46 are testis-enriched and encode a transmembrane protein which is conserved from amphibians to mammals. Loss of the mouse TEX46 protein causes male sterility primarily due to abnormal sperm head formation and secondary effects on sperm motility. Tex46 null spermatozoa morphologically lack the typical hooked sperm head appearance and fail to penetrate through the ZP. Electron microscopy of the testicular germ cells reveals malformation of the acrosomal cap, with misshapen sperm head tips and the appearance of a gap between the acrosome head and the nucleus. TEX46 is essential for sperm head formation, sperm penetration through the ZP, and male fertility in mice, and is a putative contraceptive target in men.
Investigative fatigue: how sleep-circadian factors shape criminal investigations
Authors: Krizan Zlatan , Jones Matthew
Published: March 2024

Investigating criminal complaints and identifying culprits to be prosecuted in the court of law is an essential process for law-enforcement and public safety. However, law-enforcement investigators operate under very challenging conditions due to stressful environments, understaffing, and public scrutiny, which factors into investigative errors (e.g. uncleared cases). This paper argues that one contributing factor to investigative failures involves sleep and circadian disruption of investigators themselves, known to be prevalent among law-enforcement. By focusing on investigative interviewing, this analysis illustrates how sleep and circadian disruption could impact investigations by considering three broad phases of (1) preparation, (2) information elicitation, and (3) assessment and corroboration. These phases are organized in a framework that outlines theory-informed pathways in need of empirical attention, with special focus on effort and decision-making processes critical to investigations. While existing evidence is limited, preliminary findings support some elements of investigative fatigue. The paper concludes by placing investigative fatigue in a broader context of investigative work while providing recommendations for future research throughout.

This paper is part of the Sleep and Circadian Health in the Justice System Collection.
Establishing an infrastructure to optimize the integration of genomics into research: Results from a precision health needs assessment
Authors: Allen Caitlin G , Bouchie Gwendolyn , Judge Daniel P , Coen Emma , English Sarah , Norman Samantha , Kirchoff Katie , Ramos Paula S , Hirschhorn Julie , Lenert Leslie , McMahon Lori L
Published: March 2024

Researchers across the translational research continuum have emphasized the importance of integrating genomics into their research program. To date capacity and resources for genomics research have been limited; however, a recent population-wide genomic screening initiative launched at the Medical University of South Carolina in partnership with Helix has rapidly advanced the need to develop appropriate infrastructure for genomics research at our institution. We conducted a survey with researchers from across our institution (n = 36) to assess current knowledge about genomics health, barriers, and facilitators to uptake, and next steps to support translational research using genomics. We also completed 30-minute qualitative interviews with providers and researchers from diverse specialties (n = 8). Quantitative data were analyzed using descriptive analyses. A rapid assessment process was used to develop a preliminary understanding of each interviewee’s perspective. These interviews were transcribed and coded to extract themes. The codes included types of research, alignment with precision health, opportunities to incorporate precision health, examples of researchers in the field, barriers, and facilitators to uptake, educational activity suggestions, questions to be answered, and other observations. Themes from the surveys and interviews inform implementation strategies that are applicable not only to our institution, but also to other organizations interested in making genomic data available to researchers to support genomics-informed translational research.
Laterally Protruded Cephalomedullary Nail Lag Screws are a Source of Consistent Thigh Pain After Pertrochanteric Fracture
Authors: Güven Şahan , Naldöven Ömer Faruk , Alkan Hilmi , Erdoğan Yasin , Çepni Şahin , Veizi Enejd
Published: March 2024

OBJECTIVES:

To assess the correlation between the amount of proximal screw lateralization and clinical symptoms in patients treated with a cephalomedullary nail (CMN) after a pertrochanteric fracture.

METHODS:

Design:

Retrospective study.

Setting:

Level 1 trauma center.

Patient Selection Criteria:

Patients operated for a pertrochanteric fracture (OTA/AO A1, A2, A3) between 2019 and 2022 and treated with a CMN were included.

Outcome Measures and Comparisons:

Three measurements were evaluated: D1 distance between the most laterally prominent point of the lag screw and the line tangent to the greater trochanter, D2 distance between the lateral femoral cortex and the most laterally prominent point of the lag screw, and D3 distance between the point where the lag screw emerges at the lateral edge of the femur shaft and the skin's surface. Clinical scores and information regarding lateral thigh pain were obtained, and a correlation analysis was performed.

RESULTS:

Mean age of the study cohort (n = 134) was 77.9 ± 12.3 years. Patients with categorical protrusion (considered present in cases where the distance between the lateral tip of the lag screw and the lateral border of the greater trochanter was ≥0.2 mm) had significantly higher rates of lateral thigh pain (P = 0.007) and discomfort while lying on the side (P = 0.032) compared with those without protrusion. Correlation analyses showed a positive correlation between measurements D1 and D2 and lateral thigh pain (r = 0.324 and r = 0.334, respectively, P < 0.001) and a negative correlation between D3 and lateral thigh pain (r = −0.286, P = 0.001). Regression analysis showed that higher D1 and D2 distances and shorter D3 distances are risk factors for lateral thigh pain (P = 0.001, 0.001, and 0.002, respectively).

CONCLUSIONS:

Increasing lateral protrusion of the lag screw leads to significantly greater clinical complaints and lateral hip pain in patients treated with a CMN. Patients with lower distance between the lateral femoral wall and the skin are at higher risk of lateral pain.

LEVEL OF EVIDENCE:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Tranexamic Acid in Upper Gastrointestinal Bleeding is Associated With Venous and Arterial Thromboembolic Events
Authors: Fowler Cosmo , Nasser Jason , Fera Brittany , Chism Lauren , Pastores Stephen M.
Published: March 2024

OBJECTIVES:

To determine the risk difference of arterial and venous thromboembolic events between patients with upper gastrointestinal bleeding (UGIB) who received and did not receive tranexamic acid.

DESIGN:

Retrospective cohort study.

SETTING:

The TriNetX Analytics (Cambridge, MA) Research Network, a deidentified mixed electronic health record and claims-derived database with over 110 million patients, primarily located in the United States.

PATIENTS:

A total of 2,016,763 patients diagnosed with hematemesis or melena between October 31, 2003, and October 31, 2023.

INTERVENTIONS:

Receipt of tranexamic acid within 7 days of a UGIB diagnosis.

MEASUREMENTS AND MAIN RESULTS:

We measured the incidence of thromboembolic events, both venous (deep venous thrombosis [DVT] and pulmonary embolism [PE]) and arterial (cerebrovascular accident [CVA] and myocardial infarction [MI]), within either 7 days of tranexamic acid (for recipients) or 7 days of UGIB diagnosis (for nonrecipients). Subsequently, we developed similar subcohorts using propensity score matching (PSM) for demographic and comorbidity data and reexamined the incidence of thromboembolic events, both before and after excluding any patients with any prior episodes of the outcomes. In all analyses, tranexamic acid recipients experienced significantly more adverse thromboembolic outcomes, with the post-PSM cohorts’ risk difference generating an odds ratio of 1.4 for MI (95% CI, 1.2–1.7), 1.6 in CVA (95% CI, 1.3–1.9), 1.8 in PE (95% CI, 1.5–2.3), and 2.1 in DVT (95% CI, 1.8–2.5); all p values of less than 0.001.

CONCLUSIONS:

Leveraging data from a large, multi-institutional database, we identified a correlation between tranexamic acid use in patients with UGIB and the occurrence of both venous and arterial thromboembolic events. Although the former is well-attested in the literature, the latter finding is more novel, underscoring the need for further prospective research to better characterize the risk-benefit profile of tranexamic acid in the management of gastrointestinal bleeding.
COVID-19 and the Impact on Delirium Care of Hospitalized Older Adults
Authors: Byrnes Tru , Pate Kimberly , Belin Latasia , Weaver Kelley Jo A. , Cochran Allyson
Published: March 2024

Background:

Older adult patients with COVID-19 and delirium experience higher rates of adverse outcomes. Early recognition of at-risk patients and implementation of management strategies improve outcomes, though understanding barriers to acute care nurses implementing these strategies is limited.

Purpose:

This study's purpose was to understand the experiences of acute care nurses providing care to older adults with COVID-19 and delirium. Experiences explored included assessment, nursing management interventions, and barriers to care.

Methods:

Purposive sampling to recruit nurses for semistructured focus groups was performed, and thematic analysis was generated by 4 members of the research team.

Results:

Twenty-one nurses participated in focus groups. Thematic analysis revealed themes of increased patient social isolation, barriers to delirium assessment and prevention, increased staff demands, and stressful work environments.

Conclusion:

Rich findings reveal the profound impact of the pandemic on assessment for delirium and implementation of strategies for prevention and management in older adult patients.
Comparison of Outcomes after Autologous Breast Reconstruction: Latissimus Dorsi with Immediate Fat Transfer versus Abdominally Based Free Flaps
Authors: Spoer Daisy L. , Berger Lauren E. , Huffman Samuel S. , Lava Christian X. , Dekker Paige K. , Ko JiMin A. , Truong Brian N. , Towfighi Parhom N. , Ghyasi Niloofar , Fan Kenneth L. , Song David H.
Published: March 2024

Background:

Autologous breast reconstruction confers favorable patient reports of satisfaction and quality of life compared with implant-based reconstruction over a lifetime. The latissimus dorsi with immediate fat transfer (LIFT) is an alternative approach to abdominally based free flaps (Ab-FF), which expands fully autologous reconstruction to nonmicrosurgeons. This study compared the 2 procedures concerning their clinical and patient-reported outcomes 1 year postoperatively.

Methods:

The authors conducted a retrospective review of LIFTs and Ab-FFs performed between March of 2017 and August of 2022. The primary outcomes were postoperative complications, reoperations, and longitudinal BREAST-Q scores. BREAST-Q modules included Satisfaction with Breasts, Satisfaction with Abdomen, Satisfaction with Back, Psychosocial Well-being, Physical Well-being: Chest, Physical Well-being: Abdomen, Physical Well-being: Back, and Sexual Well-being.

Results:

Of the 281 included patients (408 breasts), 211 received Ab-FF and 70 received LIFT. One-year follow-up (median [interquartile range], 12 [12] months) demonstrated that Ab-FF independently predicted dehiscence, reoperation procedures, and revisional surgery. LIFT independently increased the odds of seroma. Obesity predicted dehiscence, and bilateral reconstructions predicted revisional fat grafting. BREAST-Q scores fluctuated over time but were similar across all measured domains by 1 year postoperatively.

Conclusions:

Although Ab-FF is the standard approach for fully autologous reconstruction, LIFT procedures may be associated with a less complicated postoperative course while eliciting similar patient-reported outcomes. LIFT may be preferred to limit postoperative complications, particularly in patients with obesity. LIFT can be used by plastic surgeons who are not trained in microsurgical procedures or do not have an environment that fosters Ab-FF.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Targeting Macrophages in Organ Transplantation: A Step Toward Personalized Medicine
Authors: Owen Macee C. , Kopecky Benjamin J.
Published: March 2024

Organ transplantation remains the most optimal strategy for patients with end-stage organ failure. However, prevailing methods of immunosuppression are marred by adverse side effects, and allograft rejection remains common. It is imperative to identify and comprehensively characterize the cell types involved in allograft rejection, and develop therapies with greater specificity. There is increasing recognition that processes mediating allograft rejection are the result of interactions between innate and adaptive immune cells. Macrophages are heterogeneous innate immune cells with diverse functions that contribute to ischemia-reperfusion injury, acute rejection, and chronic rejection. Macrophages are inflammatory cells capable of innate allorecognition that strengthen their responses to secondary exposures over time via “trained immunity.” However, macrophages also adopt immunoregulatory phenotypes and may promote allograft tolerance. In this review, we discuss the roles of macrophages in rejection and tolerance, and detail how macrophage plasticity and polarization influence transplantation outcomes. A comprehensive understanding of macrophages in transplant will guide future personalized approaches to therapies aimed at facilitating tolerance or mitigating the rejection process.
Meropenem resistant Burkholderia pseudomallei - A concerning single case in Australia with no prior meropenem exposure
Authors: Sivabalan Pirathaban , Satyaputra Ferris , Gassiep Ian , Forde Brian , Frazer Jaimie , Glover Matthew , Adams Buenafe , Norton Robert
Published: March 2024

We report a case of cutaneous melioidosis in a 54-year-old male with a meropenem resistant sub-population. He was empirically treated with episodic doxycycline and trimethoprim-sulfamethoxazole, however the abscess re-accumulated. The patient had no prior exposure to meropenem. A sub-population of the isolate was meropenem resistant with an MIC>32 µg/ml and the identification was re-confirmed as B. pseudomallei. Whole genome sequencing with ARDaP analysis only revealed a resistance determinant to doxycycline and it didn’t reveal a resistance determinant to meropenem. Furthermore, no carbapenemases were detected through multiple bioinformatics tools. To date this is the first reported case in Australia of a B. pseudomallei isolate resistant to meropenem without previous carbapenem exposure.
Emerging challenge of Linezolid and Vancomycin resistant Enterococci faecium:First case report from Northern Pakistan
Authors: Naeem Afnan , Furqan Warda , Satti Luqman , Usman Javaid , Wattoo Nasir Mehmud
Published: March 2024

Enterococcus faecium are among the most versatile pathogens found to infect hospitalized patients. Resistance against anti-enterococcal antibiotics is gaining access day to day and among them linezolid resistant vancomycin resistant Enterococcus faecium are a nightmare for the clinicians especially in a resource limited country.
A 72year old patient presented with collection of pus and necrosis around the head of pancreases. These pockets of pus resulted as acute postsurgical complication along with surgical site infection. Pus was processed according to clinical guidelines Enterococcus faecium was identified and confirmed by VITEK. Isolate was resistant to vancomycin and linezolid. Tigecyclin was the only option for this patient due to unavailability of quinupristin/dalfopristin as a treatment option. A regular follow up was done and patient was discharged after recovery.
LRVRE is the result of non-implementation of antimicrobial stewardship and it can be followed with further resistance in Enterococcus which can be havoc. Clinicians infection control team and microbiologist should work together to overcome antimicrobial resistance crises.
Ecosystem Links: Macrophytes, Snail Preferences, and Trematode Transmission in Man-Made Water Bodies
Authors: Mudavanhu Aspire , Goossens Emilie , Schols Ruben , Manyangadze Tawanda , Nhiwatiwa Tamuka , Huyse Tine , Brendonck Luc
Published: March 2024

Freshwater snails act as obligate intermediate hosts for trematode parasites that cause trematodiases threatening public and veterinary health, and biodiversity conservation. Therefore, interest has re-emerged in snails as a target for disease control, yet their ecology is poorly understood. We studied the relationship between physical and chemical water parameters, macroinvertebrates, macrophytes, land use, and snail abundance, diversity, and infection rate in man-made reservoirs in eastern Zimbabwe. We observed no significant relationship between water quality parameters or macroinvertebrates and snail communities, but a significant association existed between specific macrophytes and snail species. Schistosome-competent snails (i.e.,Biomphalaria pfeifferiand bulinids) were most associated with emergentCladium mariscus,whereasPhysella acutawas associated with submerged oxygen weed,Lagarosiphon major. This offers a possibility to incorporate the management of macrophytes in integrated snail control schemes. Diversity of freshwater snail species significantly varied across land use types with the lowest observed diversity in the commercial tobacco farm section, dominated by invasive exoticP. acutaandPseudosuccinea columella, as compared to the less impacted conserved area, reflecting the adverse effects of agriculture on biodiversity. Out of the 547 schistosome host snails, 88 were shedding cercariae (16.1%) of various types, including schistosomes and amphistomes. We did not find any significant associations between macroinvertebrate or macrophyte diversity and snails and their infection rate.
Rice OsPLATZ3 controls ROS homeostasis by inhibiting ROS-Scavenging Activity during Tapetum Degeneration
Authors: Li Yuanya , Wang Jing , Tang Fengxian , Li Lin , Cheng Xingyu , Sun Xialing , Yu Shuangshuang , Xia Pan , Wang Yuxiang , Tong Mingyang , Cheng Lizhong
Published: March 2024

OsPLATZ3, a transcription factor of rice (Oryza sativa) belonging to the PLATZ family, is involved in the repression of transcriptional activity.PLATZ3exhibits preferential expression in the tapetal cells during anthers development, regulating tapetum degeneration by controlling the dynamics of reactive oxygen species (ROS) in rice male reproductive processes. TheOsplatz3exhibits enlarged tapetum with delayed degeneration, significantly lower ROS levels from S5 to S12 in anthers compared to the wild-type, resulting in complete male sterility. In the anthers ofOsplatz3, there are significant changes in the regulators of programmed cell death (PCD)-induced tapetal degradation, such asTDR,EAT1, and their effectorsOsCP1,OsC6,OsAP25, andOsAP37. These findings indicate thatOsPLATZ3is a new addition to the tapetum PCD regulatory network. In the late stages of anthers development,Osplatz3exhibits phenotypes associated with oxidative stress. Transcriptome analysis revealed significant differential expression in 229 genes associated with maintaining ROS homeostasis. Furthermore, Electrophoretic Mobility Shift Assay (EMSA) demonstrate that OsPLATZ3 can bind to the promoter region ofOsAPX9, a gene encoding a plant ascorbate peroxidase domain protein with putative ROS scavenging capabilities. These findings suggest that OsPLATZ3 serves as a crucial regulatory factor in tapetum PCD by suppressing ROS scavenging activity.
Towards Efficientk-Mer Set Operations via Function-Assigned Masked Superstrings
Authors: Sladký Ondřej , Veselý Pavel , Břinda Karel
Published: March 2024

The design of efficient dynamic data structures for largek-mer sets belongs to central challenges of sequence bioinformatics. Recent advances in compactk-mer set representations via simplitigs/Spectrum-Preserving String Sets, culminating with the masked superstring framework, have provided data structures of remarkable space efficiency for wide ranges ofk-mer sets. However, the possibility to perform set operations remained limited due to the static nature of the underlying compact representations. Here, we developf-masked superstrings, a concept combining masked superstrings with custom demasking functionsfto enablek-mer set operations based on index merging. Combined with the FMSI index for masked superstrings, we obtain a memory-efficientk-mer membership index and compressed dictionary supporting set operations via Burrows-Wheeler Transform merging. The framework provides a promising theoretical solution to a pressing bioinformatics problem and highlights the potential off-masked superstrings to become an elementary data type fork-mer sets.

2012 ACM Subject Classification

Applied computing→Bioinformatics; Theory of computation→Pattern matching

Funding

Ondřej Sladký: Supported by GA ČR project 22-22997S and ERC-CZ project LL2406 of the Ministry of Education of Czech Republic.

Pavel Veselý: Supported by GA ČR project 22-22997S, ERC-CZ project LL2406 of the Ministry of Education of Czech Republic, and Center for Foundations of Modern Computer Science (Charles Univ. project UNCE 24/SCI/008).

Karel Břinda: Supported by French National Research Agency (ANR) under Grant ANR-24-CE451226 for the REALL project.
ADrosophilamodel to screen Alport syndromeCOL4A5variants for their functional pathogenicity
Authors: Duan Jianli , Wen Pei , Zhao Yunpo , van de Leemput Joyce , Yee Jennifer Lai , Fermin Damian , Warady Bradley A , Furth Susan L , Ng Derek K , Sampson Matthew G , Han Zhe
Published: March 2024

Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes (COL4A3/4/5) with most localized inCOL4A5. Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We usedDrosophila, an established model for kidney disease, and identifyCol4a1as the functional homolog of humanCOL4A5in the fly nephrocyte (equivalent of human podocyte). Fly nephrocytes deficient forCol4a1showed an irregular and thickened basement membrane and significantly reduced nephrocyte filtration function. This phenotype was restored by expressing human reference (wildtype)COL4A5, but not byCOL4A5carrying any of three established pathogenic patient-derived variants. We then screened seven additional patientCOL4A5variants; their ClinVar classification was either likely pathogenic or of uncertain significance. The findings support pathogenicity for four of these variants; the three others were found benign. Thus, demonstrating the effectiveness of thisDrosophilain vivo kidney platform in providing the urgently needed variant-level functional validation.

SUMMARY STATEMENT

Drosophila, an established model of kidney disease, was used to develop an in vivo functional screen to determine causation forCOL4A5genetic variants linked to Alport syndrome, a progressive nephropathy.
FGF21 deletion mildly exacerbates hepatic dysfunction in MASH diet and alcohol fed rats
Authors: Aldiss Peter , Nielsen Malte Hasle , Burm Hayley , Oró Denise , Hansen Henrik H. , Feigh Michael , Gillum Matthew P
Published: March 2024

Objective

Fibroblast growth factor 21 (FGF21) is a hepatokine that improves dyslipidemia, steatosis, inflammation, and fibrosis. FGF21 analogues are in clinical development as treatments for metabolic and alcohol-associated liver disease, creating a need for new models to help understand FGF21 physiology and drug mechanisms of action. The aim of this study was to create and initially characterize the first FGF21 knockout (KO) rat line to validate its utility as a translational animal model that recapitulates human MASH and ALD, and to provide a resource for examining FGF21-related phenotypes that are more appropriate for the rat.

Methods

We generated an FGF21 KO rat model using CRISPR/Cas9 to insert an artificial STOP codon in exon 1 and exposed 6-month-old WT and KO rats to either chow (n=8 per genotype) or the GAN (Gubra Amylin NASH) diet (n=16 per genotype) for 12 weeks. We further evaluated alcohol drinking behavior and biochemistry in FGF21 KO and WT rats. In the diet model, we further analysed liver and blood biochemistry in addition to histopathological scoring of NAFLD activity score (NAS), fibrosis stage and the liver transcriptome for in-depth characterization of the model.

Results

Lack of endogenous FGF21 increased plasma transaminases, liver weight, and total levels of liver TG in GAN-fed FGF21 KO rats. FGF21 deletion also increased ALT in alcohol-fed FGF21 KO rats. However, in the GAN diet model, FGF21 KO had no impact on body weight, fat mass, glycaemic traits, MASH histological endpoints including hepatic steatosis, NAS score, lobular inflammation, ballooning degeneration or fibrosis stage after 12 weeks. Similarly, there was no effect of the loss of endogenous FGF21 on the liver transcriptome in response to GAN diet feeding. Finally, we demonstrate that endogenous FGF21 does not regulate drinking behaviour in rats.

Conclusion

FGF21 deficiency accelerates hepatic dysfunction in diet and alcohol-induced liver disease models in rats, providing support from a new species that FGF21 might be a hepatoprotective factor.
Adaptive trade-offs between vertebrate defense and insect predation drive ant venom evolution
Authors: Touchard Axel , Robinson Samuel D. , Lalagüe Hadrien , Ascoët Steven , Billet Arnaud , Dejean Alain , Téné Nathan J. , Petitclerc Frédéric , Troispoux Valérie , Treilhou Michel , Bonnafé Elsa , Vetter Irina , Vizueta Joel , Moreau Corrie S. , Orivel Jérôme , Tysklind Niklas
Published: March 2024

Stinging ants have diversified into various ecological niches, and several evolutionary drivers may have contributed to shape the composition of their venom. To comprehend the drivers underlying venom variation in ants, we selected 15 Neotropical species and recorded a range of traits, including ecology, morphology, and venom bioactivity. Principal component analysis of both morphological and venom bioactivity traits revealed that stinging ants display two functional strategies. Additionally, phylogenetic comparative analysis indicated that venom function (predatory, defensive, or both) and mandible morphology significantly correlate with venom bioactivity and amount, while pain-inducing activity trades off with insect paralysis. Further analysis of the venom biochemistry of the 15 species revealed switches between cytotoxic and neurotoxic venom compositions in some species. This study highlights the fact that ant venoms are not homogenous, and for some species, there are major shifts in venom composition associated with the diversification of venom ecological functions.

Significance

Venoms are under severe evolutionary pressures, exerted either on the innovation of toxins or the reduction of the metabolic cost of production (1). To reduce the metabolic costs associated with venom secretion, some venomous animals can regulate venom expenditure by metering the amount of venom injected and by switching between offensive and defensive compositions (2–2). Many ants use venom for subduing a wide range of arthropod prey, as well as for defensive purposes against invertebrates and vertebrates, but are unable to adapt venom composition to stimuli (5, 6). Consequently, the expression of venom genes directly affects the ability of ants to interact with the biotic environment, and the venom composition may be fine-tuned to the ecology of each species. A previous study showed that defensive traits in ants exhibit an evolutionary trade-off in which the presence of a sting is negatively correlated with several other defensive traits, further supporting that trade-offs in defensive traits significantly constrain trait evolution and influence species diversification in ants (7). However, the sting is not used for the same purpose depending on the ant species. Our study supports an evolutionary trade-off between the ability of venom to deter vertebrates and to paralyze insects which are correlated with different life history strategies among Formicidae.
A change incis-regulatory logic underlying obligate versus facultative muscle multinucleation in chordates
Authors: Johnson Christopher J. , Zhang Zheng , Zhang Haifeng , Shang Renjie , Piekarz Katarzyna M. , Bi Pengpeng , Stolfi Alberto
Published: March 2024

Vertebrates and tunicates are sister groups that share a common fusogenic factor, Myomaker (Mymk), that drives myoblast fusion and muscle multinucleation. Yet they are divergent in when and where they express Mymk. In vertebrates, all developing skeletal muscles express Mymk and are obligately multinucleated. In tunicates, Mymk is only expressed in post-metamorphic multinucleated muscles, but is absent from mononucleated larval muscles. In this study, we demonstrate thatcis-regulatory sequence differences in the promoter region ofMymkunderlie the different spatiotemporal patterns of its transcriptional activation in tunicates and vertebrates. While in vertebrates Myogenic Regulatory Factors (MRFs) like MyoD1 alone are required and sufficient forMymktranscription in all skeletal muscles, we show that transcription ofMymkin post-metamorphic muscles of the tunicateCionarequires the combinatorial activity of MRF/MyoD and Early B-Cell Factor (Ebf). This macroevolutionary difference appears to be encoded incis,likely due to the presence of a putative Ebf binding site adjacent to predicted MRF binding sites in theCiona Mymkpromoter. We further discuss howMymkand myoblast fusion might have been regulated in the last common ancestor of tunicates and vertebrates, for which we propose two models.
NEK1haploinsufficiency worsens DNA damage but not defective ciliogenesis inC9ORF72patient-derived iPSC-motoneurons
Authors: Santangelo Serena , Invernizzi Sabrina , Sorce Marta Nice , Casiraghi Valeria , Peverelli Silvia , Brusati Alberto , Colombrita Claudia , Ticozzi Nicola , Silani Vincenzo , Bossolasco Patrizia , Ratti Antonia
Published: March 2024

A hexanucleotide G4C2repeat expansion (HRE) inC9ORF72gene is the major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to both loss- and gain-of-function pathomechanisms. The wide clinical heterogeneity amongC9ORF72patients suggests potential modifying genetic factors. Notably,C9ORF72mutations often co-occur with other variants in ALS/FTD-associated genes, such asNEK1, which encodes for a kinase involved in multiple pathways including DNA damage response and ciliogenesis. In this study, we generated induced pluripotent stem cells (iPSCs) and differentiated motoneurons (iPSC-MNs) derived from an ALS patient carrying bothC9ORF72HRE and aNEK1loss-of-function mutation to study the effect of theNEK1haploinsufficiency onC9ORF72pathology. Double mutantC9ORF72/NEK1cells showed increased pathologicalC9ORF72RNA foci in iPSCs and higher DNA damage levels in iPSC-MNs compared to single mutantC9ORF72cells. In contrast, ciliogenesis was similarly impaired in bothC9ORF72andC9ORF72/NEK1iPSC-MNs showing shorter cilia. Altogether, our study supports the use of patient-derived iPSCs to functionally explore the contribution of genetic modifiers inC9ORF72-associated pathology.