bluuebunny/crossref_metadata_2025 huggingface dataset:
The Primacy of Hope for Human Flourishing
Authors: Jeffrey Anne , Mehari Krista
Published: May 2023

In this paper we argue that the eudaimonist virtue of hope holds pride of place in development of psychological traits that promote human flourishing. The argument is part theoretical and part empirical. On the theoretical side, hope, the virtue, is the disposition to envision future good possibilities for oneself and one’s community and to move towards those possibilities. This renders hope necessary for any agent’s self-conscious pursuit of the goods that constitute flourishing, and also for the development of other virtues. On the empirical side, we draw on evidence from psychology to argue that early in development, humans need relationships of trust with caregivers to develop the future orientation and features of agency constitutive of the virtue of hope. Thus the virtue of hope generally needs to be fostered, in part, through trusting relationships for humans to flourish.
Alterations of ribosomal RNA pseudouridylation in human breast cancer
Authors: Barozzi Chiara , Zacchini Federico , Corradini Angelo Gianluca , Morara Monica , Serra Margherita , De Sanctis Veronica , Bertorelli Roberto , Dassi Erik , Montanaro Lorenzo
Published: May 2023

RNA modifications are key regulatory factors for several biological and pathological processes. They are abundantly represented on ribosomal RNA (rRNA), where they contribute to regulate ribosomal function in mRNA translation. Altered RNA modification pathways have been linked to tumorigenesis as well as to other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern in rRNA in breast cancer samples exploiting the RBS-Seq technique involving RNA bisulfite treatment coupled with a new NGS approach. We found a wide variability among patients at different sites. The most dysregulated positions in tumors turned out to be hypermodified with respect to a reference RNA. As for 2′O-methylation level of rRNA modification, we detected variable and stable pseudouridine sites, with the most stable sites being the most evolutionary conserved. We also observed that pseudouridylation levels at specific sites are related to some clinical and bio-pathological tumor features and they are able to distinguish different patient clusters. This study is the first example of the contribution that newly available high-throughput approaches for site specific pseudouridine detection can provide to the understanding of the intrinsic ribosomal changes occurring in human tumors.
A case of malignant mesothelioma in a young patient with childhood leukaemia who had received total body irradiation
Authors: Hayat Redwan , Ahmed Saad , Badiger Rekha , Lee Shi Han , Peryt Adam , Gilligan David , Khalid Zubair
Published: May 2023

This case report explores a 34-year-old male diagnosed with mesothelioma who had no known risk factors. The patient initially was treated for empyema with antibiotics but later represented to hospital with worsening symptoms. He underwent a surgical Video-assisted thoracoscopic surgery procedure and lung biopsy, which revealed a diagnosis of mesothelioma. The young age of the patient as well as absence of significant risk factors for mesothelioma made the diagnosis unexpected. The patient had total body irradiation (TBI) therapy for leukaemia as a child, which increases the risk of developing cancer. However, there are limited studies exploring the risk of pleural mesothelioma post-TBI. Young patients who represent to hospital, with limited response to initial treatment, and suspicious radiological features should be considered for lung biopsy to reduce the risk of a missed diagnosis. Patients with a background of TBI should also be considered for follow-up to monitor for any subsequent malignancy.
Unusual case of adult-onset cutaneous lupus erythematosus mimicking early mycosis fungoides
Authors: Ahmed Hanof , Petkar Mahir , Wafi Omar , Abu Shaikha Samya
Published: May 2023

Discoid lupus erythematosus (DLE) is a chronic variant of cutaneous lupus erythematous developing on sun-exposed areas in multi-morphic forms making diagnosis challenging. Clinical suspicion and prompt treatment are necessary to avoid permanent disfigurement, progression to systemic involvement and poor quality of life. We report a case of delayed DLE diagnosis in a 45-year-old man who presented with a new skin lesion mimicking the early stages of mycosis fungoides that prompted further investigation. Histopathological examination confirmed DLE and appropriate treatment was initiated. However, the atypical clinical presentation led to disseminated DLE and refractory disease control, resulting in scarring and cosmetic disfigurement.
Multivariate analysis compares and evaluates drought and flooding tolerances of maize germplasm
Authors: Wang Guo Yun , Ahmad Shakeel , Wang Yong , Wang Bing Wei , Huang Jing Hua , Jahan Mohammad Shah , Zhou Xun Bo , Shi Cheng Qiao
Published: May 2023

Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological mechanisms and accurate evaluation indicators and methods of maize germplasm involved in drought and flooding stresses. The twice replicated pot experiments with 60 varieties, combined with the field validation experiment with 3 varieties, were conducted under well-watered, drought, and flooding conditions. Most varieties exhibited stronger tolerance to drought than flooding due to higher antioxidant enzyme activities, osmotic adjustment substances, and lower reactive oxygen species. In contrast, flooding stress resulted in higher levels of reactive oxygen species (particularly O2−), ascorbate peroxidase, catalase, peroxidase, and soluble sugars but lower levels of superoxide dismutase, proline, and soluble protein compared with well-watered conditions. Superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, proline, soluble sugars, and protein contents, in addition to plant height, leaf area/plant, and stem diameter, were accurate and representative indicators for evaluating maize tolerance to drought and flooding stresses and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. A total of 4 principal components were extracted, in which different principal components played a vital role in resisting different water stresses. Finally, the accuracy of the 3 varieties screened by multivariate analysis was verified in the field. This study provides insights into the different physiological mechanisms and accurate evaluation methods of maize germplasm involved in drought and flooding stresses, which could be valuable for further research and breeding.
Extracellular vesicles contribute to early cyst development in autosomal dominant polycystic kidney disease by cell‐to‐cell communication
Authors: Carotti Valentina , van Megen Wouter H. , Rigalli Juan P. , Barros Eric R. , Sommers Vera , Rutten Luco , Sommerdijk Nico , Peters Dorien J. M. , van Asbeck‐van der Wijst Jenny , Hoenderop Joost G. J.
Published: May 2023

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of fluid‐filled cysts within the kidney due to mutations in PKD1 or PKD2. Although the disease remains incompletely understood, one of the factors associated with ADPKD progression is the release of nucleotides (including ATP), which can initiate autocrine or paracrine purinergic signaling by binding to their receptors. Recently, we and others have shown that increased extracellular vesicle (EVs) release from PKD1 knockout cells can stimulate cyst growth through effects on recipient cells. Given that EVs are an important communicator between different nephron segments, we hypothesize that EVs released from PKD1 knockout distal convoluted tubule (DCT) cells can stimulate cyst growth in the downstream collecting duct (CD). Here, we show that administration of EVs derived from Pkd1−/− mouse distal convoluted tubule (mDCT15) cells result in a significant increase in extracellular ATP release from Pkd1−/− mouse inner medullary collecting duct (iMCD3) cells. In addition, exposure of Pkd1−/− iMCD3 cells to EVs derived from Pkd1−/− mDCT15 cells led to an increase in the phosphorylation of the serine/threonine‐specific protein Akt, suggesting activation of proliferative pathways. Finally, the exposure of iMCD3 Pkd1−/− cells to mDCT15 Pkd1−/− EVs increased cyst size in Matrigel. These findings indicate that EVs could be involved in intersegmental communication between the distal convoluted tubule and the collecting duct and potentially stimulate cyst growth.
Improving Racial and Ethnic Disparities in Outpatient Anterior Cervical Discectomy and Fusion Driven by Increasing Utilization of Ambulatory Surgical Centers in New York State
Authors: Amen Troy B. , Chatterjee Abhinaba , Dekhne Mihir , Rudisill Samuel S. , Subramanian Tejas , Song Junho , Kazarian Gregory , Morse Kyle , Iyer Sravisht , Qureshi Sheeraz
Published: May 2023

Study Design.

Retrospective cohort study.

Objective.

The purpose of this study was to assess trends in disparities in utilization of hospital outpatient departments (HOPDs) and ambulatory surgical centers (ASCs) for outpatient ACDF (OP-ACDF) between white, Black, Hispanic, and Asian/Pacific Islander patients from 2015-2018 in New York state.

Summary of Background Data.

Racial and ethnic disparities within the field of spine surgery have been thoroughly documented. To date, it remains unknown how these disparities have evolved in the outpatient setting alongside the rapid emergence of ASCs and whether restrictive patterns of access to these outpatient centers exist by race and ethnicity.

Methods.

We conducted a retrospective review from 2015-2018 using the Healthcare Cost and Utilization Project (HCUP) New York State Ambulatory Database. Differences in utilization rates for OP-ACDF were assessed and trended over time by race and ethnicity for both HOPDs and freestanding ASCs. Poisson regression was used to evaluate the association between utilization rates for OP-ACDF and race/ethnicity.

Results.

Between 2015-2018, Black, Hispanic, and Asian patients were less likely to undergo OP-ACDF compared to white patients in New York state. However, the magnitude of these disparities lessened over time, as Black, Hispanic, and Asian patients had greater relative increases in utilization of HOPDs and ASCs for ACDF when compared to white patients (p

trend
<0.001). The magnitude of the increase in freestanding ASC utilization was such that minority patients had higher ACDF utilization rates in freestanding ASCs by 2018 (P<0.001).

Conclusion.

We found evidence of improving racial disparities in the relative utilization of outpatient ACDF in New York state. The increase in access to outpatient ACDF appeared to be driven by an increasing number of patients undergoing ACDF in freestanding ASCs in large metropolitan areas. These improving disparities are encouraging and contrast previously documented inequalities in inpatient spine surgery.

Level of Evidence.

III
Significance of Basal Cell Carcinomas Exhibiting Intravascular Invasion
Authors: Bae Edward , Breen Catherine , Vidal Eduardo , Anderson-Dockter Heidi , Snow Stephen N. , Liu Rosemarie H. , Longley Bruce Jack , Iwamoto Satori
Published: May 2023

Intravascular invasion of tumor cells can be associated with metastasis in many cancers. Basal cell carcinomas (BCCs), however, rarely metastasize; therefore, the clinical impact of intravascularly invasive BCC (IVBCC) is currently unclear. Because of these facts and the rarity of IVBCC, questions have arisen on whether IVBCC truly exists. We present 4 cases of IVBCC: one case with obvious tumor islands within immunolabeled blood vessels in the context of advanced disease and 3 cases found incidentally during Mohs micrographic surgery. We discuss the difficulty in studying IVBCC, the idea that it could be due to artifact, and the lack of direct clinical–pathological correlation. Given these challenges, we propose diagnostic criteria for IVBCC to decrease ambiguity for pathological diagnosis. Such criteria may facilitate further studies on the clinical significance of IVBCC.
Management of Pyogenic Liver Abscesses
Authors: Lam John C. , Stokes William
Published: May 2023

Pyogenic liver abscesses (PLAs) are a suppurative infection of the hepatic parenchyma responsible for significant morbidity and mortality. PLAs are categorized into a variety of mechanisms: (1) via the portal vein, (2) through the biliary tract, (3) via the hepatic artery, (4) from trauma, (5) contiguously via direct extension, and (6) cryptogenically. The pathogenesis of PLA, which informs treatment, can often be discerned based on host factors, clinical presentation, and causative microorganisms. The Streptococcus anginosus group, hypervirulent Klebsiella pneumoniae, and multidrug-resistant gram-negative pathogens have emerged as microbiologically challenging organisms to treat. The identification of hypervirulent K. pneumoniae should prompt for assessment for metastatic spread and consideration of prolonged antimicrobial treatment. Abdominal imaging is indispensable in characterizing PLAs and facilitating source control interventions. Source control remains the most critical aspect of PLA management, followed by antimicrobial therapy. Empiric antibiotics for PLAs are informed by the suspected etiology of PLA formation. Duration of antimicrobial therapy is individualized and dependent on multiple components, including the success of achieving source control, host factors, mechanism of PLA development, and the illness course of the individual—factoring in clinical, biochemical, and radiographic parameters.
Amalgamation of Toll-Like Receptor and Hypoxic Signaling in Etiology of Preeclampsia
Authors: Aggarwal Ruby , Jain Arun Kumar , Mehta Vandana , Rath Gayatri
Published: May 2023

Inflammation and oxidative stress are involved in the pathogenesis of preeclampsia. Therefore, the aim of this study was to investigate the expression of Toll-like receptor (TLR) (TLR-4, HMGB1, NFκB, IκBα) and hypoxic (HIF-1α, HIF-1β, PHD, pVHL) pathway proteins in the placenta of preeclamptic pregnant women after 28 weeks of gestational period. A possible association between these 2 pathways was also explored. A total of 194 placental tissues of preeclamptic as well as healthy pregnant women were analyzed by immunohistochemistry. On the basis of gestational age, the samples were divided into 2 groups, I (28–36 wk) and II (36 wk onwards), with 55 and 139 samples in the respective groups. The expression of both TLR (TLR-4, HMGB1, NFκB, IκBα) and hypoxic (HIF-1α, HIF-1β, PHD, pVHL) pathway proteins were significantly modulated in the placental tissues of preeclampsia as compared with control. The 2 pathways were interlinked in preeclampsia. This study highlights the intercorrelation of both TLR and hypoxic signalling pathways that may be a causative factor for the pathophysiology of preeclampsia.
Diagnostic Utility of STAT6 and pSTAT6 Immunohistochemistry for Distinguishing Classic Hodgkin Lymphoma and Peripheral T-Cell Lymphoma With Hodgkin and Reed-Sternberg–like Cells
Authors: Satou Akira , Takahara Taishi , Yamashita Daisuke , Seki Masafumi , Kato Seiichi , Tanioka Fumihiko , Tsuyuki Takuji , Wada Eriko , Sakurai Kaneko , Karube Kennosuke , Tsuzuki Toyonori , Nakamura Shigeo
Published: May 2023

Peripheral T-cell lymphomas (PTCLs), particularly nodal lymphomas of T-follicular helper cell origin, may include Hodgkin/Reed-Sternberg (HRS)-like cells in their microenvironment. These HRS-like cells are morphologically indistinguishable from HRS cells of classic Hodgkin lymphoma (CHL). Therefore, PTCLs with HRS-like cells pose a differential diagnosis vis-à-vis CHL. A previous study reported that, in contrast to HRS cells, programmed death-ligand 1 (PD-L1) expression is rare in HRS-like cells of PTCLs and suggested that PD-L1 immunohistochemistry is useful to differentiate HRS cells and HRS-like cells. In this study, we analyzed 21 patients with PTCL with HRS-like cells and 34 patients with CHL and assessed the diagnostic utility of STAT6, pSTAT6, and pSTAT3 immunohistochemistry in distinguishing HRS cells from HRS-like cells. In addition, we also performed PD-L1 immunohistochemistry to reconfirm its utility in distinguishing the 2 diseases. Compared with HRS cells in CHLs, HRS-like cells in PTCLs showed significantly less positivity for STAT6 (9.6% vs. 70%, P<0.001), pSTAT6 (9.6% vs. 70%, P<0.001), and PD-L1 (9.6% vs. 85%, P<0.001). Thus, we reconfirmed the diagnostic utility of PD-L1 immunohistochemistry in distinguishing CHLs from PTCLs with HRS-like cells. In contrast, both HRS-like and HRS cells were highly associated with pSTAT3 expression, with no significant difference in positive cell frequency (86% vs. 91%, P=0.66). On the basis of these findings, we conclude that, in addition to PD-L1, STAT6 and pSTAT6 immunohistochemistry are helpful diagnostic tools to distinguish CHLs from PTCLs with HRS-like cells.
Impact of Tissue Expander Surface Texture on Two-Stage Breast Reconstruction Outcomes: A Combined Analysis
Authors: Park Benjamin C. , Alving-Trinh Alexandra L. , Prigmore Heather L. , Harrell Frank E. , Sarhane Karim , Joseph Jeremy T. , Thomas Harrison , Lupi Alexander L. , Perdikis Galen , Higdon Kent K.
Published: May 2023

Background:

With ongoing investigations of the impact of device texturing on breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), studies have begun comparing complication profiles of tissue expanders. However, there is a paucity of timing and severity data of complications. The aim of this study was to provide a comparative survival analysis of postoperative complications between smooth (STEs) and textured tissue expanders (TTEs) in breast reconstruction.

Methods:

A single-institution experience with tissue expander breast reconstruction was reviewed for complications up to 1 year after second-stage reconstruction from 2014 to 2020. Demographics, comorbidities, operation-related variables, and complications were evaluated. Kaplan-Meier curves, Cox proportional hazard models, and a consensus-based ordinal logistic regression model were used to compare complication profiles.

Results:

Of 919 total patients, 600 (65.3%) received TTEs and 319 (34.7%) received STEs. There was increased risk of infection (P < 0.0001), seroma (P = 0.046), expander malposition (P < 0.0001), and wound dehiscence (P = 0.019) in STEs compared with TTEs. However, there was also a decreased risk of capsular contracture (P = 0.005) in STEs compared with TTEs. Failure of breast reconstruction (P < 0.001) and wound dehiscence (P = 0.018) occurred significantly earlier in STEs compared with TTEs. Predictors for significantly higher severity complications included the following: smooth tissue expander use (P = 0.007), shorter time to complication (P < 0.0001), higher body mass index (P = 0.005), smoking history (P = 0.025), and nipple-sparing mastectomy (P = 0.012).

Conclusions:

Differences in the timing and severity of complications contribute to the safety profiles of tissue expanders. STEs are associated with increased odds of higher severity and earlier complications. Therefore, tissue expander selection may depend on underlying risk factors and severity predictors.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A Systematic Review and Revised Meta-analysis of the Effort-Reward Imbalance Model of Workplace Stress and Hypothalamic-Pituitary-Adrenal Axis Measures of Stress
Authors: Eddy Pennie , Wertheim Eleanor H. , Hale Matthew W. , Wright Bradley J.
Published: May 2023

Objective

Despite considerable research in the past 20 years into associations between the effort-reward imbalance (ERI) model and various health outcomes, the mechanisms responsible for the association remain unclear. Our meta-analysis assessed the associations of ERI and overcommitment (OC) in the workplace with measures from the hypothalamic-pituitary-adrenal (HPA) axis.

Methods

Electronic databases were searched with the phrase “effort * reward * imbalance,” which yielded 319 studies leading to 56 full-text studies being screened. Thirty-two studies within 14 articles met the inclusion criteria and were meta-analyzed using mixed- and random-effects models.

Results

Greater ERI was associated with increased HPA axis activity (r = 0.05, p = .02, k = 14, n = 2461). The cortisol waking concentrations (r = 0.11, p = .02, k = 6, n = 493) were the only subgroup associated with ERI. Meta-regression revealed that studies that contained more men had stronger ERI to HPA marker associations. When all HPA markers were considered collectively, OC was not associated with greater HPA axis activity (r = 0.01, p = .70, k = 10, n = 1684), with only cortisol (pm) associated with OC (r = −0.24, p = .02, k = 2, n = 95).

Conclusions

ERI and OC were associated with HPA responsivity. Although the cortisol waking concentrations and not the CAR were associated with ERI, this may be due to heterogeneity in the experience of stress between studies. Future studies should consider the concurrent assessment of burnout to better assist the interpretation of ERI with HPA responsivity.
Teaching Models for Correct Rhombic Flaps
Authors: Hwang Kun , Yoon Jin Myung , Park Tae Jun , Park Chan Yong
Published: May 2023

The aim of this study was to introduce teaching models for correct rhombic flaps. For the line of maximal extensibility (LME) and flap design, surgical fabric (model 1), scored corrugated cardboard (model 2), and scored polyethylene sheet (model 3) were used. For choosing the correct flaps, a silicone face (model 4) was used. Seven participants in the Plastic Surgery Department were recruited for the workshop. In models 1 to 3, a 2-cm diameter circle and relaxed skin tension line were indicated. Participants were requested to design Limberg flaps. Each flap was elevated, transposed, and fixed with sutures (model 1) or cellophane tape (models 2 and 3). In model 4, a 1-cm diameter circle was indicated on the cheek. Participants were requested to design correct Limberg flaps. Although participants were not provided an article describing how to create correct Limberg flaps, they eventually created correct flaps through trial and error. Participants drew 2 parallel lines tangential to the defect and following the LME, perpendicular to the relaxed skin tension lines, which are the same as the scoring marks. They then drew 2 other sides of 2 possible parallelograms by tilting them medially and laterally with angles of 60 and 120 degrees each. Thus, 4 possible Limberg flaps to close the defect were drawn. Among the 8 possible flaps, 4 flaps that did not follow the LME were eliminated. Scored polyethylene sheet had the best extensibility and least distortion among the 3 models. Through this workshop, participants learned to design rhombic flaps correctly, using 2 parallel LMEs.
Anterior Maxillary Distraction Osteogenesis With Bone-borne Intraoral Buccal Devices for Maxillary Hypoplasia With Cleft Lip and Palate
Authors: Yamagata Kenji , Mohri Tamaki , Watanabe Atsushi , Bukawa Moeka , Uchida Fumihiko , Fukuzawa Satoshi , Ishibashi-Kanno Naomi , Bukawa Hiroki
Published: May 2023

Anterior maxillary distraction osteogenesis (AMDO) surgery for cleft lip and palate involves distraction of a segment of the anterior maxilla and advancement using 2 intraoral buccal bone-borne distraction devices. The anterior part of the maxilla is advanced anteriorly with less relapse which increases maxillary length and does not affect speech. We aimed to evaluate the effects of AMDO, including lateral cephalometric changes. Seventeen patients who had undergone this procedure were included in this retrospective study. The distractors were activated by 0.5 mm twice a day after a 3-day latency period. Lateral cephalometric radiographs were evaluated preoperatively, after distraction and removal of distractors, which were compared using the paired Student’s t test. Anterior maxillary advancement was obtained in all patients with a median of 8.0 mm. Complications included nasal bleeding and loosening of distractors; however, there was no tooth damage or abnormal movement. The mean sella-nasion-A point (SNA) angle increased significantly, from 74.91° ﻿to 79.66°, the A point-nasion-B point angle from -0.38° to 4.34°, and the perpendicular line from nasion to Frankfort Horizontal (NV)-A point from -5.11 to 0.08 mm. The mean anterior nasal spine-posterior nasal spine length increased significantly from 50.74 to 55.10 mm, and the NV-Nose Tip from 23.59 to 26.27 mm. The mean relapse rate of NV-A was 11.1%. AMDO with bone-borne distractor resulted in less relapse and effectively ﻿corrected the maxillary retrusion.
CSF1R-related Adult-onset Leukoencephalopathy
Authors: Moreno Loscertales Cristina , Canasto Jiménez Paula , Bautista Lacambra Mario , Tique Rojas Luisa , Izquierdo Álvarez Silvia , Marta Moreno Eugenia
Published: May 2023

Colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy is a primary microgliopathy characterized by a complex phenotype, which can be easily misdiagnosed with other leukoencephalopathy and neurodegenerative diseases such as frontotemporal dementia. It is estimated to be the most common adult-onset leukodystrophy. Here, we report the case of a 67-year-old man with a history of progressive impairment of behavioral and cognitive functions, including apathy, inhibition, tendency to mutism, and deficits in complex planning skills. Neurological examination revealed pyramidalism in the lower limbs. Brain imaging showed symmetrical confluent frontal leukoencephalopathy, bilateral frontal calcifications, and thinning of the corpus callosum. The diagnosis was confirmed by the identification of a heterozygous pathogenic variant in the colony-stimulating factor 1 receptor. As far as we know, this is the first documented case in Spain. In this paper, we aim to expand on clinical features and underline the importance of brain imaging for the diagnosis of an entity that we consider to be underdiagnosed.
Gracilimonas sediminicola sp. nov., a moderately halotolerant bacterium isolated from seaweed sediment collected in the East Sea, Republic of Korea
Authors: Lee Yunjeong , Weerawongwiwat Veeraya , Kim Jong-Hwa , Yoon Jung-Hoon , Lee Jung-Sook , Sukhoom Ampaitip , Kim Wonyong
Published: May 2023

A Gram-stain-negative, aerobic, rod-shaped bacterium, designated as strain CAU 1638T, was isolated from seaweed sediment collected in the Republic of Korea. The cells of strain CAU 1638T grew at 25–37 °C (optimum, 30 °C), at pH 6.0–7.0 (optimum, pH 6.5) and in the presence of 0–10% NaCl (optimum, 2 %). The cells were positive for catalase and oxidase and did not hydrolyse starch and casein. Strain CAU 1638T was most closely related to

Gracilimonas amylolytica

KCTC 52885T (97.7 %), followed by

Gracilimonas halophila

KCTC 52042T (97.4 %),

Gracilimonas rosea

KCCM 90206T (97.2 %),

Gracilimonas tropica

KCCM 90063T and

Gracilimonas mengyeensis

DSM 21985T (97.1 %), as revealed by 16S rRNA gene sequencing. MK-7 was the major isoprenoid quinone, and iso-C15  : 0 and C15  : 1
 ω6c were the major fatty acids. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, two unidentified lipids, two unidentified glycolipids and three unidentified phospholipids. The G+C content of the genome was 44.2 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain CAU 1638T and the reference strains were 73.1–73.9 % and 18.9–21.5  %, respectively. Based on its phylogenetic, phenotypic and chemotaxonomic features, strain CAU 1638T represents a novel species of the genus

Gracilimonas

, for which the name Gracilimonas sediminicola sp. nov. is proposed. The type strain is CAU 1638T (=KCTC 82454T=MCCC 1K06087T).
Direct monitoring of meropenem therapeutic efficacy against Klebsiella pneumoniae respiratory infection by bioluminescence imaging
Authors: Fodah Ramy A. , Scott Jacob B. , Warawa Jonathan M.
Published: May 2023

Introduction.

Klebsiella pneumoniae

is a major threat to public health worldwide. It is the causative agent for multiple disease presentations including urinary tract infection, septicemia, liver abscess, wound infection and respiratory tract infection.

K. pneumoniae

causes community- and hospital-acquired pneumonia, which is a devastating disease associated with high mortality rates.

Hypothesis. There is a growing concern about the emergence of multidrug-resistant

K. pneumoniae

strains complicating the treatment with the current available therapeutics; therefore, there is an urgent need for the development of new antimicrobial agents.

Aim.

K. pneumoniae

causes an acute respiratory disease in mice and in the current work we investigated the capability to perform non-invasive monitoring of bioluminescent

Klebsiella

to monitor therapeutic efficacy.

Methodology. We engineered a bioluminescence reporter strain of

K. pneumoniae

to monitor the impact of antibiotics in a murine respiratory disease model.

Results. We demonstrate that bioluminescence correlates with bacterial numbers in host tissues allowing for a non-invasive enumeration of bacterial replication in vivo. Light production is directly linked to bacterial viability, and this novel bioluminescent

K. pneumoniae

strain enabled monitoring of the efficacy of meropenem therapy in arresting bacterial proliferation in the lung.

Conclusion. The use of non-invasive bioluminescent imaging improves preclinical animal model testing to detect study outcome earlier and with higher sensitivity.
An Explainable and Robust Deep Learning Approach for Automated Electroencephalography-based Schizophrenia Diagnosis
Authors: Sattiraju Abhinav , Ellis Charles A. , Miller Robyn L. , Calhoun Vince D.
Published: May 2023

Schizophrenia (SZ) is a neuropsychiatric disorder that affects millions globally. Current diagnosis of SZ is symptom-based, which poses difficulty due to the variability of symptoms across patients. To this end, many recent studies have developed deep learning methods for automated diagnosis of SZ, especially using raw EEG, which provides high temporal precision. For such methods to be productionized, they must be both explainable and robust. Explainable models are essential to identify biomarkers of SZ, and robust models are critical to learn generalizable patterns, especially amidst changes in the implementation environment. One common example is channel loss during EEG recording, which could be detrimental to classifier performance. In this study, we developed a novel channel dropout (CD) approach to increase the robustness of explainable deep learning models trained on EEG data for SZ diagnosis to channel loss. We developed a baseline convolutional neural network (CNN) architecture and implement our approach as a CD layer added to the baseline (CNN-CD). We then applied two explainability approaches to both models for insight into learned spatial and spectral features and show that the application of CD decreases model sensitivity to channel loss. The CNN and CNN-CD achieved accuracies of 81.9% and 80.9% on testing data, respectively. Furthermore, our models heavily prioritized the parietal electrodes and the α-band, which is supported by existing literature. It is our hope that this study motivates the further development of explainable and robust models and bridges the transition from research to application in a clinical decision support role.
Value-based search efficiency is encoded in substantia nigra reticulata firing rate, spiking irregularity and local field potential
Authors: Narmashiri Abdolvahed , Abbaszadeh Mojtaba , Nadian Mohammad Hossein , Ghazizadeh Ali
Published: May 2023

Recent results show that valuable objects can pop-out in visual search yet its neural mechanisms remain unexplored. Given the role of substantia nigra reticulata (SNr) in object value memory and control of gaze, we recorded its single unit activity while male macaque monkeys engaged in efficient or inefficient search for a valuable target object among low-value objects. Results showed that efficient search was concurrent with stronger inhibition and higher spiking irregularity in target present (TP) compared to target absent (TA) trials in SNr. Importantly, the firing rate differentiation of TP and TA trials happened within ∼100ms of display onset and its magnitude was significantly correlated with the search times and slopes (aka search efficiency). Time-frequency analyses of local field potential (LFP) after display onset revealed significant modulations of gamma band power with search efficiency. The greater reduction of SNr firing in TP trials in efficient search can create a stronger disinhibition of downstream superior colliculus which in turn can facilitate saccade to obtain valuable targets in competitive environments.

Significant statement

Most times we have to find a few relevant or highly valued objects among many objects that surround us. When our target objects are not distinct from their surroundings based on low-level features, searching for them becomes tedious and slow. Nevertheless, recent findings show that valuable objects can be found efficiently and fast if they have been repeatedly paired with reward. Our results show that the rate and pattern of spiking as well as local voltage fluctuations in the basal ganglia output which is known to control attention and saccade correlate with such value-driven search efficiency. Thus, in addition to reward learning, basal ganglia can have a role in skillful interactions with and rapid detection of rewarding objects.
Individualized network analysis reveals link between the gut microbiome, diet intervention and Gestational Diabetes Mellitus
Authors: Liu Yimeng , Amit Guy , Zhao Xiaolei , Wu Na , Li Daqing , Bashan Amir
Published: May 2023

Gestational Diabetes Mellitus (GDM), a serious complication during pregnancy which is defined by abnormal glucose regulation, is commonly treated by diabetic diet and lifestyle changes. While recent findings place the microbiome as a natural mediator between diet interventions and diverse disease states, its role in GDM is still unknown. Here, based on observation data from healthy pregnant control group and GDM patients, we developed a new network approach using patterns of co-abundance of microorganism to construct microbial networks that represent human-specific information about gut microbiota in different groups. By calculating network similarity in different groups, we analyze the gut microbiome from 27 GDM subjects collected before and after two weeks of diet therapy compared with 30 control subjects to identify the health condition of microbial community balance in GDM subjects. Although the microbial communities remain similar after the diet phase, we find that the structure of their inter-species co-abundance network is significantly altered, which is reflected in that the ecological balance of GDM patients was not "healthier" after the diet intervention. In addition, we devised a method for individualized network analysis of the microbiome, thereby a pattern is found that individuals with large deviations in microbial networks are usually accompanied by their abnormal glucose regulation. This approach may help the development of individualized diagnosis strategies and microbiome-based therapies in the future.

Author Summary

In this study, we aimed to investigate the role of the gut microbiome in gestational diabetes mellitus (GDM), a condition that affects pregnant women and is characterized by abnormal glucose regulation. Specifically, we asked whether and how the gut microbiome is affected by diabetic diet which is commonly used to treat GDM patients. We developed a new network approach to analyze patterns of co-abundance of microorganisms in the gut microbiota of GDM patients and healthy pregnant women. Our findings show that although the microbial communities remained similar after the diet phase, the structure of their inter-species co-abundance network was significantly altered, indicating that the ecological balance of GDM patients was not "healthier" after the diet intervention. Furthermore, we suggest that abnormal glucose regulation is associated with large network deviations, which could lead to the development of individualized microbiome-based therapies in the future. Our work highlights the importance of studying the microbiome from a network perspective to better understand the dynamic interactions among microorganisms in the community balance of the microbiome.
FOXK2amplification and overexpression promotes breast cancer development and chemoresistance
Authors: Yu Yang , Cao Wen-Ming , Cheng Feng , Shi Zhongcheng , Han Lili , Yi Jin-Ling , da Silva Edaise M , Dopeso Higinio , Chen Hui , Yang Jianhua , Wang Xiaosong , Zhang Chunchao , Zhang Hong
Published: May 2023

Activation of oncogenes through DNA amplification/overexpression plays an important role in cancer initiation and progression. Chromosome 17 has many cancer-associated genetic anomalies. This cytogenetic anomaly is strongly associated with poor prognosis of breast cancer.FOXK2gene is located on 17q25 and encodes a transcriptional factor with a forkhead DNA binding domain. By integrative analysis of public genomic datasets of breast cancers, we found thatFOXK2is frequently amplified and overexpressed in breast cancers. FOXK2 overexpression in breast cancer patients is associated with poor overall survival.FOXK2knockdown significantly inhibits cell proliferation, invasion and metastasis, and anchorage-independent growth, as well as causes G0/G1 cell cycle arrest in breast cancer cells. Moreover, inhibition of FOXK2 expression sensitizes breast cancer cells to frontline anti-tumor chemotherapies. More importantly, co-overexpression of FOXK2 and PI3KCA with oncogenic mutations (E545K or H1047R) induces cellular transformation in non-tumorigenic MCF10A cells, suggesting thatFOXK2is an oncogene in breast cancer and is involved in PI3KCA-driven tumorigenesis. Our study identifiedCCNE2,PDK1, and Estrogen receptor alpha (ESR1) as direct transcriptional targets of FOXK2 in MCF-7 cells. Blocking CCNE2- and PDK1-mediated signaling by using small molecule inhibitors has synergistic anti-tumor effects in breast cancer cells. Furthermore, FOXK2 inhibition by gene knockdown or inhibitors for its transcriptional targets (CCNE2 and PDK1) in combination with PI3KCA inhibitor, Alpelisib, showed synergistic anti-tumor effects on breast cancer cells with PI3KCA oncogenic mutations. In summary, we provide compelling evidence that FOXK2 plays an oncogenic role in breast tumorigenesis and targeting FOXK2-mediated pathways may be a potential therapeutic strategy in breast cancer.
CARD-like domains mediate anti-phage defense in bacterial gasdermin systems
Authors: Wein Tanita , Johnson Alex G. , Millman Adi , Lange Katharina , Yirmiya Erez , Hadary Romi , Garb Jeremy , Steinruecke Felix , Hill Aidan B. , Kranzusch Philip J. , Sorek Rotem
Published: May 2023

Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Upon pathogen recognition by NLR proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore forming proteins to and induce pyroptotic cell death. Here we show that CARD-like domains are present in defense systems that protect bacteria against phage. The bacterial CARD is essential for protease-mediated activation of certain bacterial gasdermins, which promote cell death once phage infection is recognized. We further show that multiple anti-phage defense systems utilize CARD-like domains to activate a variety of cell death effectors. We find that these systems are triggered by a conserved immune evasion protein that phages use to overcome the bacterial defense system RexAB, demonstrating that phage proteins inhibiting one defense system can activate another. We also detect a phage protein with a predicted CARD-like structure that can inhibit the CARD-containing bacterial gasdermin system. Our results suggest that CARD domains represent an ancient component of innate immune systems conserved from bacteria to humans, and that CARD-dependent activation of gasdermins is conserved in organisms across the tree of life.
Biomolecular condensates of Chlorocatechol 1,2-Dioxygenase as enzymatic microreactors for the degradation of polycyclic aromatic hydrocarbons
Authors: Evangelista Nathan N. , Micheletto Mariana C. , Mendes Luis F. S. , Costa-Filho Antonio J.
Published: May 2023

Polycyclic aromatic hydrocarbons (PAHs) are molecules with two or more fused aromatic rings that occur naturally in the environment due to incomplete combustion of organic substances. However, the increased demand for fossil fuels in recent years has increased anthropogenic activity, contributing to the environmental concentration of PAHs. The enzyme chlorocatechol 1,2-dioxygenase fromPseudomonas putida(Pp 1,2-CCD) is responsible for the breakdown of the aromatic ring of catechol, making it an interesting player in bioremediation strategies. Pp 1,2-CCD can tolerate a broader range of substrates, including halogenated compounds, than other dioxygenases. Here, we report the construction of a chimera protein able to form biomolecular condensates with potential application in bioremediation. The chimera protein was built by conjugating Pp 1,2-CCD to low complex domains (LCDs) derived from the DEAD-box protein Dhh1. We showed that the chimera could undergo liquid-liquid phase separation (LLPS), forming a protein-rich liquid droplet under different conditions (variable protein and PEG8000 concentrations and pH values), in which the protein maintained its structure and main biophysical properties. The condensates were active against 4-chlorocatechol, showing that the chimera droplets preserved the enzymatic activity of the native protein. The possible application of these microreactors in bioremediation is discussed.
Spatial autocorrelation of the environment influences the patterns and genetics of local adaptation
Authors: Booker Tom R.
Published: May 2023

Environmental heterogeneity can lead to spatially varying selection, which can, in turn, lead to local adaptation. Population genetic models have shown that the pattern of environmental variation in space can strongly influence the evolution of local adaptation. In particular, when environmental variation is highly autocorrelated in space local adaptation will more readily evolve. Despite this long-held prediction, the evolutionary genetic consequences of different patterns of environmental variation have not been thoroughly explored. In this study, simulations are used to model local adaptation to different patterns of environmental variation. The simulations confirm that local adaptation is expected to increase with the degree of spatial autocorrelation in the selective environment, but also show that highly heterogeneous environments are more likely to exhibit high variation in local adaptation, a result not previously described. Spatial autocorrelation in the environment also influences the evolution and genetic architecture of local adaptation, with different combinations of allele frequency and effect size arising under different patterns of environmental variation. These differences influence the ability to characterise the genetic basis of local adaptation in different environments. Finally, I analyse a large-scale provenance trial conducted on lodgepole pine and find suggestive evidence that spatially autocorrelated environmental variation leads to stronger local adaptation in natural populations of lodgepole pine. Overall, this work emphasizes the profound importance that the spatial pattern of selection can have on the evolution of local adaptation and how spatial autocorrelation should be considered when formulating hypotheses in ecological and genetic studies.

Lay Summary

Many species exhibit local adaptation to environmental variation across their ranges. Theoretical population genetics predicts that the evolution of local adaptation and patterns of genetic variation underlying it will be influenced by the spatial pattern of variation across a species’ range. However, this prediction has not been thoroughly explored for cases of complex heterogeneous landscapes. In this paper, I analyse simulations and empirical data to characterise the effects that the spatial pattern of environmental variation can have on the evolution of local adaptation and the genetics underlying it. From these analyses, I show that the pattern of environmental variation influences the average level of local adaptation, variation in local adaptation as well as the genetics underlying this important phenomenon.
Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
Authors: Wang Ruixiang , Khan Kanza M. , Balasubramanian Nagalakshmi , James Thomas , Pushpavathi Selvakumar Govindhasamy , Kim David , Pierson Samantha , Wu Qi , Niciu Mark J. , Hefti Marco M. , Marcinkiewcz Catherine A.
Published: May 2023

Social interaction is a core component of motivational behavior that is perturbed across multiple neuropsychiatric disorders, including alcohol use disorder (AUD). Positive social bonds are neuroprotective and enhance recovery from stress, so reduced social interaction in AUD may delay recovery and lead to alcohol relapse. We report that chronic intermittent ethanol (CIE) induces social avoidance in a sex-dependent manner and is associated with hyperactivity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN). While 5-HTDRNneurons are generally thought to enhance social behavior, recent evidence suggests that specific 5-HT pathways can be aversive. Using chemogenetic iDISCO, the nucleus accumbens (NAcc) was identified as one of 5 regions that were activated by 5-HTDRNstimulation. We then employed an array of molecular genetic tools in transgenic mice to show that 5-HTDRNinputs to NAcc dynorphin neurons drive social avoidance in male mice after CIE by activating 5-HT2Creceptors. NAcc dynorphin neurons also inhibit dopamine release during social interaction, reducing the motivational drive to engage with social partners. This study reveals that excessive serotonergic drive after chronic alcohol can promote social aversion by inhibiting accumbal dopamine release. Drugs that boost brain serotonin levels may be contraindicated for individuals with AUD.
The mediating effect of job satisfaction between inclusive leadership and commitment to change: evidence from Brazil and Spain
Authors: Gil Alfonso J. , Mosegui Gabriela , Zenezi Moreira Rosana , Eguizabal Mauro J.
Published: May 2023

Purpose

In the current context of change, leadership is significant in developing employees' commitment to change. In this work, the authors analysed the relationship between inclusive leadership and commitment to change and the mediating effect of job satisfaction between inclusive leadership and commitment to change.

Design/methodology/approach

Through a questionnaire, 256 employees from Brazil and Spain were interviewed. The hypotheses were tested through structural equations.

Findings

The results indicated that inclusive leadership is related to individuals' commitment to change and that job satisfaction mediates the relationship between leadership and commitment to change.

Originality/value

This research contributes to the literature on organisational change behaviour and the relationship between two critical contents – leadership and commitment to change – and points out the role of job satisfaction in this relationship. In addition, this work incorporates the variable country culture into the analysis model; however, it is not found to be statistically significant.