bluuebunny/crossref_metadata_2025 huggingface dataset:
(291) The Effect of Administration and Discontinuation of Finasteride in Male Rats
Authors: Lee D , Choi Y
Published: March 2024

Introduction

It has been suggested that 5AR (5-alpha reductase) inhibitors may have negative effects on psychosexual activity, but there is still debate.

Objective

We aimed to observe the effect of 5AR type 2 inhibition on brain tissue by using finasteride.

Methods

14 weeks old, eight male rats were assigned to each group (group 1 as the control group, group 2 as the finasteride group, and group 3 as the finasteride withdrawal group). Each rat was isolated and acclimatized in a single cage, then mated for 2 days. Rats in group 2 and 3 were administrated with finasteride for 4 weeks, then rats in group 2 were sacrificed whereas rats in group 3 were sacrificed 4 weeks thereafter. Before sacrifice, they were exposed to female bedding at least for 2 days. RT-PCR, western blot, and immunohistochemistry were performed for brain tissue evaluation where the target genes/proteins were 5AR (type 2) and c-Fos.

Results

Dihydrotestosterone (ng/dl) and dihydrotestosterone to testosterone ratio (%) plunged after 1 month administration of finasteride (group 2), and they were ameliorated after discontinuation of the drug (group 3) (Figure 1). These results were parallel to those from the western blot and immunohistochemistry (Figure 2 and 3). On the contraty, RT-PCR showed elevation of each gene (5AR and c-Fos) expression (Figure 2).

Conclusions

Finasteride exerted an influence on brain tissue including hippocampus and ventromedial preoptic area via 5AR-2 inhibition, resulting in decrease of c-Fos protein activation. However, the negative impact of finasteride on rat brain in regard with c-Fos activation may fall away in a month cessation of the drug.

Disclosure

No.
“A Poem Is a Gesture toward Home”: Formal Plurality and Black/Queer Critical Hope in Jericho Brown’s Duplex Form
Authors: Hoelzer Kaitlin
Published: March 2024

Jericho Brown’s The Tradition (2019), which won the Pulitzer Prize for poetry, includes four duplexes, a poetic form of Brown’s own invention that combines the sonnet and the blues. Made of fourteen lines separated into seven couplets, the duplex is a complex structure comprised of sets of indents and repeated lines. Brown’s use of disparate source forms to create a new form altogether challenges the supremacy of a singular, white American literary tradition, putting it into conversation with other traditions in order to critique its historically racist and heterosexist boundaries. As he does so, Brown works not to abolish “the tradition” or canon but to expand it beyond reductive ideas of who and what is allowed into this historically exclusive space. The complexity of Brown’s formal project mirrors the nuanced and critical hope the duplex form expresses and evokes in readers; in contrast to queer theory’s focus on negativity, Brown’s duplexes align with the work of José Muñoz and Mari Ruti, who assert that hope is equally as important as negativity. The duplex form holds the positive and negative together in both form and content, and seeks to expand emotional experience and the canon, ultimately attempting to change the way readers feel and act.
“He Hopes They Have Disappeared”: Necro-elasticity and the Tyranny of the Present in Helena María Viramontes’s “The Cariboo Cafe”
Authors: Avila Edward
Published: March 2024

This essay investigates the ways in which Helena María Viramontes’s “The Cariboo Cafe” (1985) depicts the necropolitical order of power in Central America and the United States during the decades-long civil wars (late 1970s to early 1990s) marked by racial violence and brutality committed by US-backed dictatorial regimes and police enforcement in both Central American and the United States. “The Cariboo Cafe” offers critical insights into the dialectical operations of the bio-necropolitical order of power in which the exposure to harm, injury, and death (that is, precarity) of racialized segments of the population serve to foster and secure the lives of those considered politically and, thus, ontologically relevant. The spatial and temporal dimensions of the story offer key insights into the specific ways in which necro-elasticity constitutes both spatial and temporal dispossession. Such dispossession, especially in its temporal configuration, points to the flattening of historical consciousness, what I refer to as “non-contextualization,” that ultimately underwrites the ideological conditions of possibility for the emergence and reproduction of individual and collective innocence and, thus, impunity.
Conditional and Unconditional Obligation
Authors: Fine Kit
Published: March 2024

I present a novel account of unconditional obligation and of its relationship to conditional obligation and bring this account to bear upon Chisholm's puzzle concerning contrary-to duty obligation.
Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy
Authors: Xi Chenxiang , Yan Zihui , Bai Dandan , Zhang Yalin , Wang Beiying , Han Xiaoxiao , Wu Li , Shi Xiaohui , Hu Zhiyi , Tang Ming , Su Zhongqu , Liu Yingdong , Liu Binya , Yin Jiqing , Wang Hong , Li Xiaocui , Zhang Yanping , Gao Shaorong , Liu Wenqiang
Published: March 2024

The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.
The New Black Right: A Paranoid Turn in Black Conservatism?
Authors: Brooks Marcus A
Published: March 2024

Is there a uniquely Black paranoid style of conservatism, and, if so, how is that style articulated, and what are the potential impacts on conservatism, U.S. politics, and Black people in the coming decades? Despite our theoretical understanding that Black people can support white supremacy, the literature of far-right racism assumes that all white nationalists are white, and all Black nationalists are pro-Black. To address these issues, I use qualitative content analysis of 100 YouTube videos from ten Black conservative influencers. I find there are Black conservatives who express a uniquely nationalist form of paranoid reactionaryism. This style of political rhetoric is characterized by influencers’ claims that: 1) they have experienced status loss, not as Black people, but as moral, patriotic, and Christian Americans; 2) this status loss is the result of a coordinated campaign to weaken the country, traditional values, and Chrisitan hegemony; and 3) the campaigns are carried out by ungodly and un-American people within the country and that acting against them in self-defense is a moral and patriotic necessity. These findings force us to reconsider our approach to studying racism and recognize the agency of Black people who actively promote far right and racist rhetoric.
Piercing the corporate veil—the trust connection
Authors: Singh Aditi , Turaga Anudeep
Published: March 2024

The principle of separate legal entity which forms the basic foundation of company law provides for the company as a separate legal entity. This results in the formation of a veil, so to say, that protects the liability of the directors or other related companies from incurring liability. Under the Doctrine of Piercing the Corporate Veil, the said veil can be disregarded in certain circumstances. Historically, this principle has been restricted to companies incorporated under statute. However, recently, a High Court of India applied the doctrine to a Charitable Trust which is a non-corporate body. With Courts of India not providing any contours or sound reasoning towards the extension of the doctrine to non-corporate bodies, this article examines the application of the doctrine on charitable trusts, the flaws and problems that arise from such application and the possible solutions for the same while tracing evolved and developing jurisprudence surrounding the doctrine in taxation cases and trusts.
Concurrent NRAS-BRAF variants in metastatic colorectal cancer: a Tunisian case report
Authors: Douik Hayet , Sahraoui Ghada , Jemaà Mohamed , Doghri Raoudha , Charfi Lamia , Mrad Karima
Published: March 2024

Target therapy for metastatic colorectal cancer needs the determination of KRAS, NRAS, and BRAF mutation status to identify patients resistant to anti-EGFR treatment. RAS genes (KRAS/NRAS) are mutated in 40–60% of metastatic colorectal cancer and BRAF in 5–10%. The presence of a double mutation in RAS and BRAF is rare. Therefore, RAS and BRAF mutations were considered exclusive. Herein, we describe a novel concomitant NRAS/BRAF mutation identified in a series of 865 colorectal cancer patients.
Explore & actuate: the future of personalized medicine in oncology through emerging technologies
Authors: Babu Erald , Sen Subhojit
Published: March 2024

Purpose of review

The future of medicine is aimed to equip the physician with tools to assess the individual health of the patient for the uniqueness of the disease that separates it from the rest. The integration of omics technologies into clinical practice, reviewed here, would open new avenues for addressing the spatial and temporal heterogeneity of cancer. The rising cancer burden patiently awaits the advent of such an approach to personalized medicine for routine clinical settings.

Recent findings

To weigh the translational potential, multiple technologies were categorized based on the extractable information from the different types of samples used, to the various omic-levels of molecular information that each technology has been able to advance over the last 2 years. This review uses a multifaceted classification that helps to assess translational potential in a meaningful way toward clinical adaptation.

The importance of distinguishing technologies based on the flow of information from exploration to actuation puts forth a framework that allows the clinicians to better adapt a chosen technology or use them in combination to enhance their goals toward personalized medicine.
Biochemically recurrent prostate cancer in the era of EMBARK and PSMA PET imaging: everything has changed, except the patients
Authors: Einstein David J. , Aragon-Ching Jeanny B. , Karzai Fatima , Madan Ravi A.
Published: March 2024

Purpose of review

Patients with biochemically recurrent prostate cancer (BCR) after unsuccessful curative therapies frequently have an indolent and asymptomatic disease course for years. There are no prospective data showing that treating BCR improves overall survival despite new imaging strategies and emerging therapeutic data. Managing BCR requires a unique perspective in oncology that balances toxicities and disease kinetics.

Recent findings

Prostate specific membrane antigen (PSMA) imaging is now widely available and can define subclinical disease in patients with BCR who otherwise have negative CT and bone scans, but limited data exists showing that treating PSMA-positive disease has long term impact. A phase 3 trial demonstrated that the androgen receptor pathway inhibitor enzalutamide either alone or with androgen deprivation therapy (ADT) was superior in delaying metastasis, relative to ADT alone. Survival benefits from this study remain unknown.

BCR is a heterogeneous population where overtreatment may present greater risk to patients than a disease course that is often indolent. Management of BCR should be individualized based on disease kinetics. Given the unique biology of BCR, future therapeutic research should emphasize an approach that alters disease trajectory without accompanying side effects and should explore options beyond ADT-based strategies.
Relationship Between Hand Function and Handheld Ultrasound Imaging in Inclusion Body Myositis
Authors: Black Carolyn , Cai Haibi , Shabbir Aliya , Wang Leo H.
Published: March 2024

Objective:

Ultrasound studies in inclusion body myositis (IBM) have reported a characteristic pattern of increased echointensity in the flexor digitorum profundus (FDP) with relative sparing of the flexor carpi ulnaris (FCU). We examined the relationship between echointensity of the FDP and FCU muscles and hand strength or patient-reported outcomes (PROs).

Methods:

A total of 15 patients with IBM were recruited. Ultrasound images of the FDP and FCU muscles were obtained by a point-of-care ultrasound and graded using the modified Heckmatt score. Hand grip and neutral pinch strength were measured by dynamometry. PROs were assessed by the IBM Upper Extremity Function Scale.

Results:

FDP and/or FCU modified Heckmatt score showed a significant relationship with grip, neutral pinch strength, and PROs.

Conclusions:

Point-of-care ultrasound examination of the forearm may serve as an extension of the neuromuscular examination. The semi-qualitative echointensity rating based on modified Heckmatt score seems to correlate well with the objective strength measurement and PROs.
Late Onset of Severe Demyelinating Peripheral Neuropathy in a 62-Year-Old African American Woman
Authors: Zivkovic Sasha A. , DiCapua Daniel
Published: March 2024

Hereditary neuropathies are typically associated with an early onset of symptoms, but same types of neuropathies may also manifest late, after the age 50 years. A 62-year-old African American woman presented with a 6-year history of gait unsteadiness and has been using a walker since the age 57 years after an unwitnessed fall. Gradual worsening of walking difficulties was later followed by decreased dexterity. The family history was negative for neuromuscular disorders, including neuropathy. On examination, the patient had both distal and proximal weakness with distal sensory loss to all modalities and hyporeflexia. Charcot Marie Tooth Examination Score was 12. Previous electrodiagnostic testing at the age 60 years showed severe sensorimotor demyelinating polyneuropathy with bilateral severe carpal tunnel syndrome. Genetic testing showed a homozygous pathogenic mutation in SH3TC2 gene (c.2860C>T; p.Arg954*), associated with CMT4C. CMT4C is the most common recessive demyelinating sensorimotor polyneuropathy and overall comprises 0.4%–1.7% of all patients with Charcot–Marie–Tooth disease. It is more common in French Canadians and Spanish Roma and in recent natural history study; only 1 of 56 patients was African American. This report demonstrates sporadic occurrence of CMT4C in other ethnic groups as well.
Effects of sports therapy on improvement of menopausal symptoms, psychological status, and body morphology in perimenopausal women
Authors: Kim Sun Mi , Ko Yongwoo , Kim Da Seol , Kim Na Yeon , Hwang Hyun Chan , Han Doug Hyun
Published: March 2024

Objective

The aim of this study was to increase the treatment rate of perimenopausal women by providing evidence-based nonpharmaceutical treatments through developing scientific evidence-based sports therapy and verifying its effectiveness.

Methods

In a cross-over design, a total of 33 women were assigned to two different sequences of intervention: sports therapy and telephone intervention (n = 17) or telephone intervention and sports therapy (n = 16). A self-reported clinical symptom survey was conducted before and after the experimental and control periods using the following measures: the Menopause Rating Scale, Patient Health Questionnaire 9, and Patient Health Questionnaire 15.

Results

There were significant differences in the changes in the scores for Menopause Rating Scale total (exercise phase, 17.8 ± 5.5 at baseline [B] and 13.5 ± 4.2 at follow-up [F]; control phase, 15.9 ± 6.0 [B] and 15.4 ± 5.3 [F]; P < 0.01), somatic symptoms (exercise phase, 9.5 ± 2.6 [B] and 6.6 ± 2.0 [F]; control phase, 8.5 ± 2.8 [B] and 8.0 ± 1.3 [F], P < 0.01), and urogenital symptoms (exercise phase, 4.9 ± 1.7 [B] and 4.1 ± 1.4 [F]; control phase, 4.3 ± 1.6 [B] and 4.4 ± 1.5 [F]; P < 0.01) between the exercise and control phases. There were also significant differences in the changes in the scores for PHQ-9 (exercise phase, 4.6 ± 4.4 [B] and 3.6 ± 3.3 [F]; control phase, 4.5 ± 3.8 [B] and 5.5 ± 4.6 [F]; P = 0.008) and PHQ-15 (exercise phase, 7.2 ± 4.4 [B] and 5.5 ± 3.5 [F]; control phase, 6.8 ± 4.4 [B] and 7.2 ± 4.9 [F]; P = 0.009) between the two phases.

Conclusions

Sports therapy would improve menopause symptoms, especially somatic and urogenital symptoms. In addition, sports therapy would improve depressive moods in perimenopausal women.
Bilateral Choroidal Detachments following Novel CAR T-Cell Immunotherapy Regimen
Authors: Goblirsch Timothy J , Huang Vincent , Maguire Albert , Chebolu Apoorv P
Published: March 2024

Purpose:

To describe a vision-threatening adverse event of a novel CAR T-cell immunotherapy for metastatic prostate cancer.

Methods:

Observational Case Report.

Patient:

77-year-old male with history of metastatic prostate cancer and pulmonary embolism enrolled in a clinical trial investigating the use of CAR T-cell immunotherapy for treatment of metastatic prostate cancer presented with a subjective left temporal visual disturbance.

Results:

The patient was found to have bilateral extensive choroidal detachments on examination. OCT macula demonstrated no intraretinal fluid or supraretinal fluid in both eyes. B-scan of both eyes redemonstrated choroidal detachments in both eyes and no retinal detachment in either eye. The patient was initiated on a topical and systemic steroid regimen and experienced symptomatic and clinical improvement.

Conclusion:

We exhibit a case of bilateral choroidal detachments secondary to systemic reaction to a novel immunotherapy for metastatic cancer successfully treated with systemic and topical steroids. Close follow up may be required for patients receiving similar novel immunotherapeutic regimens.
Severe Recurrence and Retinal Inflammatory Infiltration After Cessation of Immunosuppression for Multifocal Choroiditis and Panuveitis
Authors: Norel Jeannette Ossewaarde-van , Spaide Richard F.
Published: March 2024

Purpose:

To describe a severe recurrence of intraocular inflammation following the cessation of immunosuppression, previously administered for multifocal choroiditis and panuveitis (MCP).

Methods:

Retrospective chart review.

Results:

A 27-year-old woman with MCP initially was treated with intravenous and oral corticosteroids and photodynamic therapy because of an active macular neovascularization in both eyes. Mycophenolate was soon started and the recurrences during tapering of the oral corticosteroids in the first months were treated with periocular corticosteroids and anti-vascular endothelial growth factor injections as they became available. After a decade of immunosuppression without recurrences, the patient, having relocated, discontinued mycophenolate upon the advice of a new ophthalmologist who diagnosed her with punctate inner choroidopathy. This led to a severe recurrence in both eyes, characterized by new inflammatory lesions, ellipsoid zone loss, and widespread inflammatory cell infiltration into the outer retina. Intravitreal triamcinolone injections resulted in the resolution of sub- and intraretinal inflammatory lesions and ellipsoid zone defects.

Conclusion:

The abrupt discontinuation of immunosuppression in a patient with MCP was associated with a rebound phenomenon, characterized by multi-level inflammatory activity in the posterior pole. This rebound phenomenon may offer clues as to the inflammatory targets in MCP.
Opioid Prescribing Patterns Following Lateral Skull Base Spontaneous Cerebrospinal Fluid Leak Repair
Authors: Ottinger Allie M. , Raymond Mallory J. , Miller E. Marin , Meyer Ted A.
Published: March 2024

Objective

To characterize the opioid prescribing patterns for and requirements of patients undergoing repair of spontaneous cerebrospinal fluid (sCSF) leaks of the lateral skull base.

Study Design

Retrospective chart review.

Setting

Tertiary referral center.

Patients

Adults with lateral skull base sCSF leaks who underwent repairs between September 1, 2014, and December 31, 2020.

Main Outcome Measure

Mean morphine milligram equivalents (MMEs) of opioids dispensed to inpatients and prescribed at discharge, additional pain control medications dispensed, and outpatient additional opioid requests were compared between groups.

Results

Of 78 patients included, 46 (59%) underwent repair via a transmastoid (TM), 6 (7.7%) via a middle cranial fossa (MCF), and 26 (33.3%) via a combined TM–MCF approach. Inpatients received a mean of 21.3, 31.4, and 37.6 MMEs per day during admission for the TM, MCF, and combined TM–MCF approaches, respectively (p = 0.019, ηp2 = 0.101). Upon discharge, nearly all patients (n = 74, 94.9%) received opioids; 27.3, 32.5, and 37.6 MMEs per day were prescribed after the TM, MCF, and TM–MCF approaches, respectively (p = 0.015, ηp2 = 0.093). Five (6.4%) patients requested additional outpatient pain medication, after which three were prescribed 36.7 MMEs per day. Patients with idiopathic intracranial hypertension required significantly more inpatient MMEs than those without (41.5 versus 25.2, p = 0.02, d = 0.689), as did patients with a history of headaches (39.6 versus 23.6, p = 0.042, d = 0.684).

Conclusions

Patients undergoing sCSF leak repair via the MCF or TM–MCF approaches are prescribed more opioids postoperatively than patients undergoing the TM approach. Patients with a history of headaches or idiopathic intracranial hypertension might require more opioids postoperatively.
A Scoping Review of Otologic Manifestations of Hematologic Malignancies
Authors: Raymond Mallory J. , Ottinger Allie , Rowley M. Andrew , Bobian Michael , Dornhoffer Jim , Brennan Emily , Rizk Habib G.
Published: March 2024

Objective

To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed.

Results

Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%).

Conclusion

Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.
Novel and recurrent variants in PAX6 in four patients with ocular phenotypes from Southeast Asia
Authors: Goh Jeannette , Wei Heming , Lai Angeline H.M. , Chang Benjamin , Khan Shazia , Syn Yamon , Jamuar Saumya S. , Tan Ene-Choo
Published: March 2024

Aniridia is an autosomal dominant condition characterized by the complete or partial absence of the iris, often with additional presentations such as foveal hypoplasia, nystagmus, cataract, glaucoma and other ocular abnormalities. Most cases are caused by heterozygous mutations in the paired box 6 gene (PAX6), which codes for a transcription factor that regulates eye development. Four patients from our hospital who presented with ocular phenotypes were recruited for research sequencing with informed consent. Sanger sequencing of PAX6 coding exons or exome sequencing was performed on genomic DNA from venous blood samples. Variants in PAX6 were identified in the four patients. Two variants are recurrent single-nucleotide substitutions – one is a substitution found in a patient with bilateral aniridia, whereas the other is a splice variant in a patient with nystagmus and neuroblastoma. The other two variants are novel and found in two patients with isolated aniridia. Both are small duplications that are predicted to lead to premature termination. For the recurrent variants, the comparison of phenotypes for patients with identical variants would shed light on the mechanisms of pathogenesis, and the discovery of two novel variants expands the spectrum of PAX6 mutations.
Risk of Malignancy in Incidentally Detected Lung Nodules in Patients Aged Younger Than 35 Years
Authors: Byrne Suzanne C. , Peers Caroline , Gargan Mary Louise , Lacson Ronilda , Khorasani Ramin , Hammer Mark M.
Published: March 2024

Background

The risk of malignancy in pulmonary nodules incidentally detected on computed tomography (CT) in patients who are aged younger than 35 years is unclear.

Objective

The aim of this study was to evaluate the incidence of lung cancer in incidental pulmonary nodules in patients who are 15–34 years old.

Methods

This retrospective study included patients aged 15–34 years who had an incidental pulmonary nodule on chest CT from 2010 to 2018 at our hospital. Patients with prior, current, or suspected malignancy were excluded. A chart review identified patients with diagnosis of malignancy. Incidental pulmonary nodule was deemed benign if stable or resolved on a follow-up CT at least 2 years after initial or if there was a medical visit in our health care network at least 2 years after initial CT without diagnosis of malignancy.

Receiver operating characteristic curve analysis was performed with nodule size. Association of categorical variables with lung cancer diagnosis was performed with Fisher exact test, and association of continuous variables was performed with logistic regression.

Results

Five thousand three hundred fifty-five chest CTs performed on patients aged 15–34 years between January 2010 and December 2018. After excluding patients without a reported pulmonary nodule and prior or current malignancy, there were a total of 779 patients. Of these, 690 (89%) had clinical or imaging follow-up after initial imaging. Of these, 545 (70% of total patients) patients had imaging or clinical follow-up greater than 2 years after their initial imaging.

A malignant diagnosis was established in 2/779 patients (0.3%; 95% confidence interval, 0.1%–0.9%). Nodule size was strongly associated with malignancy (P = 0.007), with area under the receiver operating characteristic curve of 0.97. There were no malignant nodules that were less than 10 mm in size. Smoking history, number of nodules, and nodule density were not associated with malignancy.

Conclusions

Risk of malignancy for incidentally detected pulmonary nodules in patients aged 15–34 years is extremely small (0.3%). There were no malignant nodules that were less than 10 mm in size. Routine follow-up of subcentimeter pulmonary nodules should be carefully weighed against the risks.
Policies and Practices Regarding Preparative Fasting for Contrast-Enhanced Computed Tomography: A Nationwide Survey
Authors: Li Jianjie , Cai Li , Zhao Li , Liu Junling , Lan Fang , Li Yuan , Liu Heng , Li Xue
Published: March 2024

Objectives

To evaluate current policies and practices regarding preparative fasting before contrast-enhanced computed tomography (CECT) and the knowledge and attitudes of radiology head nurses.

Methods

Radiology head nurses in 499 Chinese hospitals participated in an online survey on preparative fasting for CECT, which mainly included current departmental policies and practices and their knowledge and attitudes.

Results

Response rate was 89.8% (448/499). All surveyed hospitals established preparative fasting protocols, mainly based on guidelines for iodinated contrast media (ICM) usage (68.8%). For the nongastrointestinal CECT scan, the most frequent fasting duration for solid food, semiliquid diet, liquid diet, and clear liquids was 4 to 6 hours (215/422 [50.9%]), less than 6 hours (332/396 [83.8%]), less than 6 hours (275/320, 85.9%), and less than 6 hours (151/189 [79.9%]), respectively. Forty-six percent of the respondents confirmed that unnecessary excessive fasting existed in practice, and the related patient discomfort occurred in 60.3% of the hospitals, mainly manifested as hypoglycemia (86.7%). Expert consensus and guidelines for iodinated contrast media usage (75%) were the leading approach to gain knowledge about preparative fasting; 90.6% of the respondents believed that the clinical scenarios requiring preparative fasting were the upper abdominal examinations. A majority of respondents (72.1%) believed that the current preparative fasting policies needed improvement.

Conclusion

Preparative fasting policies varied among hospitals in terms of the fasting content and duration. Respondents' opinions differed on fasting requirements based on various CECT examination sites and patients. The latest guideline regarding no fasting before CECT has not been fully adopted. Further research is required to promote the transformation of guideline evidence.
Erythrobacter oryzae sp. nov., isolated from rice paddy soil
Authors: Lee Hyo-Jin , Hwang Ji-Soo , Lee Eun-kyung , Whang Kyung-Sook
Published: March 2024

Two novel bacterial strains, designated as COR-2T and CR-8, were isolated from paddy soil. These isolates were aerobic, Gram-stain-negative, non-spore-forming, non-motile, rod-shaped, and formed orange-coloured colonies. Phylogenetic analysis based on 16S rRNA gene sequences showed that two strains formed a clear phylogenetic lineage with the genus Erythrobacter. Strains COR-2T and CR-8 showed 99.9 % 16S rRNA gene sequence similarity. Both strains had the highest 16S rRNA gene similarity of 99.1–99.7 % to Erythrobacter colymbi TPW-24T, Erythrobacter donghaensis SW-132T and Erythrobacter tepidarius DSM 10594T, respectively. The genome of strain COR-2T comprised 3 559 918 bp and the genomic DNA G + C content was 67.7 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain COR-2T and its closely related species of the genus Erythrobacter were 79.3–85.5% and 24.1–29.1 %, respectively. The major respiratory quinone was Q-10, while the major fatty acids were C18 : 1
 ω7c and C17 : 1
 ω6c. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified phospholipids and eight unidentified lipids. Based on phylogenetic and phenotypic considerations, the two strains [COR-2T (type strain; = KACC 22941T=JCM 35529T) and CR-8 (= KACC 22945=JCM 35530)] are considered to represent novel species of the genus Erythrobacter, for which the name Erythrobacter oryzae sp. nov. is proposed.
Molecular hydrogen for outpatients with Covid-19 (Hydro-Covid): a phase 3, randomised, triple-blinded, adaptive, placebo-controlled, multicentre trial
Authors: Gaboreau Yoann , Milovančev Aleksandra , Rolland Carole , Eychenne Claire , Alcaraz Jean-Pierre , Ihl Cordelia , Mazet Roseline , Boucher François , Vermorel Celine , Ostojic Sergej M. , Borel Jean Christian , Cinquin Philippe , Bosson Jean-Luc ,   the HydroCovid Investigators
Published: March 2024

Background

Due to its antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic gas for acute coronavirus disease 2019 (COVID-19) patients.

Aim

To determine the efficacy and safety profile of hydrogen rich water (HRW) to reduce the risk of progression of COVID-19.

Design and settings

We conducted a phase 3, triple-blind, randomized, placebo-controlled trial to evaluate treatment with HRW started within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19 and at least one risk factor for severe COVID-19 illness.

Method

Participants were randomly assigned to receive HRW or placebo twice daily for 21 days. The composite primary endpoint was the incidence of clinical worsening (dyspnea, fatigue) associated with a need for oxygen therapy, hospitalization or death at day-14; the incidence of adverse events was the primary safety end point.

Results

A total of 675 participants were followed up until day-30. 337 in the HRW group and 338 in the placebo group. Baseline characteristics were similar in the two groups. HRW was not superior to placebo in preventing clinical worsening at day-14: in H2group, 46.1% met a clinical deterioration, 43.5% in the placebo group, Hazard Ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported in the H2group and 2 in the placebo group at day-30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants respectively.

Conclusion

Twice-daily ingestion of HRW from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening.

How this fits in

Only a few molecules specially developed against SARS-CoV-2 can limit impact of COVID-19 (vaccines, monoclonal antibodies or antiviral drugs)

Using their multiple properties, H2 may play a key role in preventing the severe and post-acute forms of COVID-19

Taking twice daily Hydrogen Rich Water (HRW) was not efficacious to prevent severe COVID-19 in at risk COVID-19 patients.

HRW confirmed a very safe profil
Improving Heart Disease Probability Prediction Sensitivity with a Grow Network Model
Authors: Akter Simon Bin , Hasan Rakibul , Akter Sumya , Hasan Md. Mahadi , Sarkar Tanmoy
Published: March 2024

The traditional approaches in heart disease prediction across a vast amount of data encountered a huge amount of class imbalances. Applying the conventional approaches that are available to resolve the class imbalances provides a low recall for the minority class or results in imbalance outcomes. A lightweight GrowNet-based architecture has been proposed that can obtain higher recall for the minority class using the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. A Synthetic Refinement Pipeline using Adaptive-TomekLinks has been employed to resolve the class imbalances. The proposed model has been tested in different versions of BRFSS datasets including BRFSS 2022, BRFSS 2021, and BRFSS 2020. The proposed model has obtained the highest specificity and sensitivity of 0.74 and 0.81 respectively across the BRFSS 2022 dataset. The proposed approach achieved an Area Under the Curve (AUC) of 0.8709. Additionally, applying explainable AI (XAI) to the proposed model has revealed the impacts of transitioning from smoking to e-cigarettes and chewing tobacco on heart disease.
An integrative approach to protein sequence design through multiobjective optimization
Authors: Hong Lu , Kortemme Tanja
Published: March 2024

With recent methodological advances in the field of computational protein design, in particular those based on deep learning, there is an increasing need for frameworks that allow for coherent, direct integration of different models and objective functions into the generative design process. Here we demonstrate how evolutionary multiobjective optimization techniques can be adapted to provide such an approach. With the established Non-dominated Sorting Genetic Algorithm II (NSGA-II) as the optimization framework, we use AlphaFold2 and ProteinMPNN confidence metrics to define the objective space, and a mutation operator composed of ESM-1v and ProteinMPNN to rank and then redesign the least favorable positions. Using the multistate design problem of the foldswitching protein RfaH as an in-depth case study, we show that the evolutionary multiobjective optimization approach leads to significant reduction in the bias and variance in RfaH native sequence recovery, compared to a direct application of ProteinMPNN. We suggest that this improvement is due to three factors: (i) the use of an informative mutation operator that accelerates the sequence space exploration, (ii) the parallel, iterative design process inherent to the genetic algorithm that improves upon the ProteinMPNN autoregressive sequence decoding scheme, and (iii) the explicit approximation of the Pareto front that leads to optimal design candidates representing diverse tradeoff conditions. We anticipate this approach to be readily adaptable to different models and broadly relevant for protein design tasks with complex specifications.

Author summary

Proteins are the fundamental building blocks of life, and engineering them has broad applications in medicine and biotechnology. Computational methods that seek to model and predict the protein sequence-structure-function relationship have seen significant advancement from the recent development in deep learning. As more models become available, it remains an open question how to effectively combine them into a coherent computational design approach. One approach is to perform computational design with one model, and filter the design candidates with the others. In this work, we demonstrate how an optimization algorithm inspired by evolution can be adapted to provide an alternative framework that outperforms the post hoc filtering approach, especially for problems with multiple competing design specifications. Such a framework may enable researchers to more effectively integrate the strengths of different modeling approaches to tackle more complex design problems.
The power and limits of predicting exon-exon interactions using protein 3D structures
Authors: Liebold Jeanine , Del Moral-Morales Aylin , Manalastas-Cantos Karen , Tsoy Olga , Kurtz Stefan , Baumbach Jan , Newaz Khalique
Published: March 2024

Alternative splicing (AS) effects on cellular functions can be captured by studying changes in the underlying protein-protein interactions (PPIs). Because AS results in the gain or loss of exons, existing methods for predicting AS-related PPI changes utilize known PPI interfacing exon-exon interactions (EEIs), which only cover ∼5% of known human PPIs. Hence, there is a need to extend the existing limited EEI knowledge to advance the functional understanding of AS. In this study, we explore whether existing computational PPI interface prediction (PPIIP) methods, originally designed to predict residue-residue interactions (RRIs), can be used to predict EEIs. We evaluate three recent state-of-the-art PPIIP methods for the RRI- as well as EEI-prediction tasks using known protein complex structures, covering ∼230,000 RRIs and ∼27,000 EEIs. Our results provide the first evidence that existing PPIIP methods can be extended for the EEI prediction task, showing F-score, precision, and recall performances of up to ∼38%, ∼63%, and ∼28%, respectively, with a false discovery rate of less than 5%. Our study provides insights into the power and limits of existing PPIIP methods to predict EEIs, thus guiding future developments of computational methods for the EEI prediction task. We provide streamlined computational pipelines integrating each of the three considered PPIIP methods for the EEI prediction task to be utilized by the scientific community.
A Targeted Genome-scale Overexpression Platform for Proteobacteria
Authors: Banta Amy B. , Myers Kevin S. , Ward Ryan D. , Cuellar Rodrigo A. , Place Michael , Freeh Claire C. , Bacon Emily E. , Peters Jason M.
Published: March 2024

Targeted, genome-scale gene perturbation screens using Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) and activation (CRISPRa) have revolutionized eukaryotic genetics, advancing medical, industrial, and basic research. Although CRISPRi knockdowns have been broadly applied in bacteria, options for genome-scale overexpression face key limitations. Here, we develop a facile approach for genome-scale gene overexpression in bacteria we call, “CRISPRtOE” (CRISPR transposition and OverExpression). We create a platform for comprehensive gene targeting using CRISPR-associated transposition (CAST) and show that transposition occurs at a higher frequency in non-transcribed DNA. We then demonstrate that CRISPRtOE can upregulate gene expression in Proteobacteria with medical and industrial relevance by integrating synthetic promoters of varying strength upstream of target genes. Finally, we employ CRISPRtOE screening at the genome-scale in Escherichia coli, recovering known antibiotic targets and genes with unexplored roles in antibiotic function. We envision that CRISPRtOE will be a valuable overexpression tool for antibiotic mode of action, industrial strain optimization, and gene function discovery in bacteria.
Communityassesses differential cell communication using large multi-sample case-control scRNAseq datasets
Authors: Solovey Maria , Celik Muhammet A. , Salcher Felix R. , Abdalfattah Mohmed , Ismail Mostafa , Scialdone Antonio , Ziemann Frank , Colomé-Tatché Maria
Published: March 2024

Cell-cell communication is essential for physiological tissue function. In disease, this communication often gets disbalances by changes in the tissue cell type composition, fraction of cell engaged in communication and the rising or dropping expression levels of ligands, receptors and adhesion molecules. The changes in all these components of communication can be studied using single cell RNA-sequencing (scRNAseq) methods. With dropping sequencing costs, it is now possible to perform scRNAseq studies in larger cohorts of case and control samples to better address the heterogeneity of diseases. Here we presentcommunity, an R-based tool that is designed to perform differential communication analysis using scRNAseq between large cohorts of cases and controls.Communityis able to reconstruct communication between different cell types both in the case and the control cohort of a dataset, and subsequently analyze which communication channels are affected in disease.Communityis the first tool that integrates cell type abundance into the calculation of an interaction strength.Communityis also able to disentangle the mechanisms underlying these changes, as well as detect interactions that are kept compensated by a sender or a receiver despite the disbalanced signaling from the counterpart. We testedcommunityon two disease entities, ulcerative colitis and acute myeloid leukemia, using published scRNAseq datasets. We compared the performance of our tool to other differential communication pipelines, whichcommunityoutperformed in speed and robustness. Overall,communityis a fast, well-scalable, user-friendly R tool to assess differential cell-cell communication using large case-control scRNAseq datasets disentangling the driving mechanisms of communication shifts in disease.
Temporal dynamics of color processing measured using a continuous tracking task
Authors: Barnett Michael A. , Chin Benjamin M. , Aguirre Geoffrey K. , Burge Johannes , Brainard David H.
Published: March 2024

We characterized the temporal dynamics of color processing using a continuous tracking paradigm by estimating temporal impulse response functions associated with tracking chromatic Gabor patches. We measured how the lag of these functions changes as a function of chromatic direction and contrast for stimuli in the LS cone contrast plane. In the same set of subjects, we also measured detection thresholds for stimuli with matched spatial, temporal, and chromatic properties. We created a model of tracking and detection performance to test if a common representation of chromatic contrast accounts for both measures. The model summarizes the effect of chromatic contrast over different chromatic directions through elliptical isoresponse contours, the shapes of which are contrast independent. The fitted elliptical isoresponse contours have essentially the same orientation in the detection and tracking tasks. For the tracking task, however, there is a striking reduction in sensitivity to signals originating in the S cones. The results are consistent with common chromatic mechanisms mediating performance on the two tasks, but with task-dependent relative weighting of signals from L and S cones.
Molecular control of temporal integration matches decision-making to motivational state
Authors: Gautham Aditya K. , Miner Lauren E. , Franco Marco N. , Thornquist Stephen C. , Crickmore Michael A.
Published: March 2024

Motivations bias our responses to stimuli, producing behavioral outcomes that match our needs and goals. We describe a mechanism behind this phenomenon: adjusting the time over which stimulus-derived information is permitted to accumulate toward a decision. As a Drosophila copulation progresses, the male becomes less likely to continue mating through challenges. We show that a set of Copulation Decision Neurons (CDNs) flexibly integrates information about competing drives to mediate this decision. Early in mating, dopamine signaling restricts CDN integration time by potentiating CaMKII activation in response to stimulatory inputs, imposing a high threshold for changing behaviors. Later into mating, the timescale over which the CDNs integrate termination-promoting information expands, increasing the likelihood of switching behaviors. We suggest scalable windows of temporal integration at dedicated circuit nodes as a key but underappreciated variable in state-based decision-making.
Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods
Authors: Temmar Hisham , Willsey Matthew S. , Costello Joseph T. , Mender Matthew J. , Cubillos Luis H. , Lam Jordan LW , Wallace Dylan M , Kelberman Madison M. , Patil Parag G. , Chestek Cynthia A.
Published: March 2024

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by ‘decoding’ neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks.

Teaser

A neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.