bluuebunny/crossref_metadata_2025 huggingface dataset:
Repairing the harm caused by arrest: A mixed-methods evaluation of a restorative justice diversion program
Authors: Dunlap Brenna , Huff Jessica , Tregle Brandon
Published: June 2024

Research has yet to establish whether restorative justice can rebuild relationships between communities and the police. The current study examines a novel diversion program centred around police officer and arrestee restorative justice conferences. The two-year evaluation uses interviews with police officers and arrestees and surveys of arrestees to assess participants’ perceptions of the program and each other. Both groups were satisfied with the program and highly supported its continuation. Participants recognized the feelings or situations of others and humanized them. Both groups reported intentions to change their behaviours in future encounters, with officers intending to improve communication and arrestees discussing avoidance. Arrestees maintained neutral or somewhat positive perceptions of police. Arrestees in the second year had more positive perceptions of legitimacy, police interactions, and procedural justice than protesters arrested in year one. The results suggest that conferences could be a promising approach for agencies seeking to rebuild strained police–community relations.
Qualities of will and ambivalent moral worth
Authors: Eichhorn Leonie
Published: June 2024

On many prominent accounts, moral praise- and blameworthiness depend on the quality of will an agent manifests in their action. This paper draws attention to a pertinent but overlooked phenomenon: the manifestation of commendable and objectionable qualities of will in an action at once. By showing that all the manifested qualities of will have an effect on the agent's praise- and blameworthiness (i.e., on their action's moral worth), it is argued that quality of will theories need to provide an account of this effect. An account according to which the manifested degrees of qualities of will cancel each other out and the praise- or blameworthiness is determined by the remaining quality of will is discussed and dismissed. Finally, it is argued that agents who manifest objectionable and commendable qualities of will at once are simultaneously both praise- and blameworthy for their actions. Actions can thus have ambivalent moral worth.
What Is Early Recovery of Physical Abilities After Wedge Resection Surgery for Patients With Bone Tumor? An Observational Study
Authors: Cotti Marco , Morri Mattia , Peccerillo Vincenzo , Guerrini Clizia , Abbruzzese Alida , Ruggiero Antonio , Culcasi Antonio , Donati Davide Maria , Davoli Fabio , Celli Guglielmo
Published: June 2024

Background:

The aim of this study is to describe the course of recovery of physical ability for patients undergoing lung wedge resection surgery for bone tumor metastases using the 1-minute sit-to-stand (1MSTS) test.

Methods:

All patients undergoing wedge resection for localized lung metastases from January 2022 to July 2023 were recruited consecutively. The recovery of physical performance was assessed by conducting the 1MSTS test the day before surgery and every day after surgery. A comparison was made between the number of repetitions performed in the preoperative test vs the performance on the sixth postoperative day.

Results:

A total of 52 patients were enrolled. The median age was 51 years and women made up 44.2% of the sample. The 1MSTS test on the sixth day was conducted in all patients with a median number of repetitions of 17.5, with a value comparable to the preoperative median. The patients able to recover to the preoperative repetitions were 38%. Multivariate analysis showed female gender as a protective factor and previous respiratory comorbidities and previous surgery to the upper limbs/trunk as risk factors. During preoperative assessment, higher heart rate and lower oxygen saturation (SpO2) after 1MSTS test were also predictors of a worse postoperative outcome.

Conclusion:

After wedge resection surgery for lung metastasis, the recovery of physical ability should be encouraged from the early postoperative phases and can be monitored through the use of the 1MSTS test during hospitalization. Aerobic training exercises in the preoperative phase may be useful to improve preoperative performance.
Examining the Impact of the Innovative Opioid Court Model on Treatment Access and Court Outcomes for Court Participants
Authors: Elkington Katherine S. , Ryan Margaret E. , Basaraba Cale , Dambreville Renald , Alschuler Dan , Wall Melanie M. , Garcia Alejandra , Christofferson Monica , Andrews Howard F. , Nunes Edward V.
Published: June 2024

Objective

The opioid intervention court (OIC) is an innovative, pre-plea treatment court to facilitate rapid linkage to medications for opioid use disorder (MOUD) for people at risk of overdose. This study compares participants in OIC and participants with opioid use problems in a traditional drug treatment court model on (i) initiation for any substance use (SU) treatment, (ii) initiation of MOUD, (iii) number of days to MOUD initiation, and (iv) retention in the OIC program/retention on MOUD.

Methods

We used administrative court records from n = 389 OIC and n = 229 drug court participants in 2 counties in New York State. Differences in outcomes by court were assessed using logistic, multinomial, or linear regressions.

Results

After adjusting for current charge severity, gender, race/ethnicity, age, and county, OIC participants were no more likely to initiate any SU treatment but were significantly more likely to initiate MOUD (81.2% OIC vs 45.9% drug court, P < 0.001) and were more quickly linked to any SU treatment (hazard ratio = 1.68, 95% confidence interval = 1.35–2.08) and MOUD (hazard ratio = 4.25, 95% confidence interval = 3.23–5.58) after starting the court. Retention in court/MOUD was higher among drug court participants and may speak to the immediate sanctions (eg, jail) for noncompliance with drug court directives as compared with opioid court, which does not carry such immediate sanctions for noncompliance.

Conclusions

These analyses suggest that the new OIC model can more rapidly link participants to treatment, including MOUD, as compared with traditional drug court model, and may demonstrate improved ability to immediately stabilize and reduce overdose risk in court participants.
Standard Versus Rapid Inpatient Methadone Titration for Pregnant Patients With Opioid Use Disorder: A Retrospective Cohort Study
Authors: Iyer Neel S. , Ferguson Emily B. , Yan Vivian Z. , Hand Dennis J. , Abatemarco Diane J. , Boelig Rupsa C.
Published: June 2024

Objectives

Our study evaluated if rapid inpatient titration of methadone for pregnant patients with opioid use disorder (OUD) improved outcomes without increasing the risk for overdose.

Methods

This is a retrospective cohort study of pregnant patients admitted for inpatient methadone titration from January 2020 to June 2022. Outcomes were compared between standard versus rapid titration protocols. Standard titration involved an initial methadone dose with additional doses every 6 hours if clinical opiate withdrawal score (COWS) is >9. Rapid titration involved an initial methadone dose with additional doses every 4 hours if COWS is >9. The primary outcome was time required to achieve stable dose. Secondary outcomes included elopement prior to achieving stable dose, methadone-related readmission, opioid overdose, and final dose.

Results

There were 97 patients in the standard titration (STP) and 97 patients in the rapid titration (RTP) groups. Demographic characteristics and substance use history did not differ between the 2 groups. Time to stable dose did not differ between the 2 groups (RTP, 5.0 days ±4.0; STP, 4.0 days ±3.0; P = 0.08). Patients in the rapid titration group were less likely to elope from the hospital prior to stabilization (RTP 23.0% vs STP 37.9%, P = 0.03) and had fewer methadone-related readmissions (P < 0.001). One patient (1.0%) in the RTP group required naloxone treatment while inpatient for concern for overdose, while none did in the STP group (P = 0.32). There was no difference in median final stable dose between the 2 groups (P = 0.07).

Conclusions

Rapid titration of methadone for pregnant patients with OUD was associated with decreased medical elopement and methadone-related readmission, without increasing the risk for overdose.
Exploring the clinical significance of specific immune-related adverse events in melanoma patients undergoing immune checkpoint inhibitor therapy
Authors: Asher Nethanel , Bar-Hai Neta , Ben-Betzalel Guy , Stoff Ronen , Grynberg Shirly , Schachter Jacob , Frommer-Shapira Ronnie
Published: June 2024

Several studies have demonstrated that patients who experience immune-related adverse events (irAE) as a result of immunotherapy treatment, exhibit significantly improved outcomes compared to patients without toxicity. Data regarding the impact of specific irAE is, however, currently lacking. This is a real-world single-site cohort of 415 advanced melanoma patients who were treated with immunotherapy as first-line between 2014 and 2020, with a median follow-up of 24.5 months. The most frequent irAEs were cutaneous (classified as non-vitiligo, n = 110, 26.5% and vitiligo, n = 48, 11.6%), rheumatologic (n = 68, 16.4%), gastrointestinal (n = 66, 15.9%), endocrine (n = 61, 14.7%), and hepatitis (n = 50, 12%). Specific irAE that were significantly associated with survival benefit were rheumatologic (hazard ratio 0.34 for PFS, P < 0.001; hazard ratio 0.38 for OS, P < 0.001), non-vitiligo cutaneous (hazard ratio 0.58 for PFS, P < 0.001; hazard ratio 0.54 for OS, P = 0.001), vitiligo (hazard ratio 0.30 for PFS, P < 0.001; hazard ratio 0.29 for OS, P < 0.001), and endocrine (hazard ratio 0.6 for PFS, P = 0.01; hazard ratio 0.52 for OS, P < 0.001). Other types if irAEs, such as colitis, hepatitis and others - do not present this correlation. . The occurrence of these specific irAEs may reflect a hyperactivated immune response and thus can serve as meaningful clinical biomarkers.
Synchronous double primary vulvar melanoma: a not so rare possibility. A clinical and dermoscopic case study
Authors: De Giorgi Vincenzo , Cecchi Giovanni , Perillo Gabriella , Zuccaro Biancamaria , Covarelli Piero
Published: June 2024

Vulvar melanoma is considered rare, but it is the second most frequent vulvar neoplasm; 2% of melanomas in women arise in the vulvar area. It is important to highlight how the characteristics of vulvar melanoma differentiate it from classic cutaneous melanoma. Vulvar melanoma has different risk factors and clinical and dermoscopic characteristics; moreover, it has a higher recurrence rate and a greater likelihood of multifocality. Here, we present a case of a 44-year-old patient with two primary vulvar melanomas located on opposite sides of her vulva. The lesions were both flat, but they had distinct clinical and dermoscopic appearances. Melanoma of the genital tract is likely the result of a multifocal disorder of the melanocytes within the mucosa that inhabit the perineal squamous epithelium. The risk factors of vulvar melanoma differ from those of classical cutaneous melanomas. Vulvar melanoma occurs in an area shielded from ultraviolet radiation; the primary risk factors include chronic inflammatory disease, genetic susceptibility, irritant agents and viral infections. This case study reveals how a close examination of the genital area is important and how dermoscopy can aid in the differential diagnosis of vulvar lesions. Inspections of the genital area should be particularly thorough if a melanoma is detected there, given the higher risk of multifocality in that part of the body.
Scarring In Utero: An Attempt to Validate With Data Unconfounded by Migration and Medical Care
Authors: Catalano Ralph , Bonham Jason , Gemmill Alison , Bruckner Tim
Published: June 2024

Background:

“Scarring in utero” posits that populations exposed to injurious stressors yield birth cohorts that live shorter lives than expected from history. This argument implies a positive historical association between period life expectancy (i.e., average age at death in year t) and cohort life expectancy (i.e., average lifespan of persons born in year t). Tests of the argument have not produced consistent results and appear confounded by autocorrelation, migration, and access to medical care. Here we test whether, as predicted by scarring in utero, sex-specific period and cohort life expectancy appear positively related among Swedes born from 1751 through 1800. If scarring has ever influenced longevity, we should detect signals of its effects in these cohorts because, unlike other populations with known life span, they aged in place and unlikely benefitted from increased access to efficacious medical care.

Methods:

We use Box–Jenkins methods to control autocorrelation and measure associations.

Results:

Contrary to the scarring hypothesis, we find an inverse association between period and cohort life expectancy. Our findings imply that, among males, variation in injurious stress on the population predicted changes in cohort life span ranging from a gain of approximately 67 weeks to a loss of about 45 weeks of life and among females from a gain of approximately 68 weeks to a loss of about 38 weeks of life.

Conclusion:

Epidemiologists trying to understand and explain temporal variation in cohort life expectancy should view the scarring argument with greater skepticism than currently found in the literature.
Exploring venous thromboembolism in colorectal surgery: A case report and current insights
Authors: Huang Pei-Yin , Liang Jin-Tung
Published: June 2024

Venous thromboembolism (VTE) is a serious complication that can lead to significant morbidity and mortality. Although the incidence of VTE is lower in the Asian population compared with Caucasians, colorectal surgery patients still face an increased risk. This review article presents a case report of a patient who developed pulmonary embolism following surgery and provides an updated evidence-based review of VTE risk assessment and prophylactic strategies in colorectal surgery.
Intereye Asymmetry as a Predictor of Progression in Patients With Untreated Keratoconus: Findings From a Longitudinal Study
Authors: Arnalich-Montiel Francisco , Ortiz-Toquero Sara , Kandel Himal , Lewis Noni , Chiong Hong Sheng , Downie Nicholas , Watson Adam , Abbondanza Marco , Watson Stephanie
Published: June 2024

Purpose:

The purpose of this study was to evaluate interocular predictors of progression in patients with untreated keratoconus.

Methods:

This is a multicenter longitudinal observational study with real-world data collected through the Save Sight Keratoconus Registry. Patients between the period of June 2000 and September 2022 were included in this study. Parameters such as patient age, sex, ocular history, visual acuity, K2, Max-K, and thinnest corneal thickness pachymetry (TCT) were analyzed.

Results:

There were 4342 untreated eyes from 2171 patients with keratoconus. A total of 333 patients showed progression of either Max-K, TCT, or both, whereas 1838 patients showed stable parameters. Factors associated with a higher incidence of progression in Max-K were younger baseline age (HR 0.96 per year older; 95% CI 0.95–0.98, P < 0.0001) and a higher baseline intereye asymmetry in Max-K (HR 1.02 per higher diopter; 95% CI 1.00–1.04, P = 0.04). A younger baseline age was the only predictor of progression in TCT (HR 0.97 per year older; 95% CI 0.95–0.99, P = 0.001).

Conclusions:

Age is the most significant predictor of progression for both corneal thinning and progression of Max-K. Interocular asymmetry in Max-K at baseline could be used as part of an algorithm for determining the risk of keratoconus progression. It is recommended that patients with higher interocular asymmetry in Max-K have a closer follow-up of both eyes as they are at a higher risk of progression.
The Nurses' Role in the Cardiac Rehabilitation Team
Authors: Lidin Matthias , Michelsen Halldora Ögmundsdottir , Hag Emma , Stomby Andreas , Schlyter Mona , Bäck Maria , Hagström Emil , Leosdottir Margret
Published: June 2024

Background

Nurses constitute a central profession in the cardiac rehabilitation (CR) team delivering comprehensive CR to individuals with cardiovascular disease. We aimed to identify specific components reflecting the nurses' role in the CR team associated with attainment of risk factor targets post myocardial infarction.

Methods

Center-level data (n = 78) was used from the Perfect-CR study, in which structure and processes applied at CR centers in Sweden (including details on the nurses' role) were surveyed. Patient-level data (n = 6755) was retrieved from the SWEDEHEART registry. Associations between structure/processes and target achievement for systolic blood pressure (BP) (<140 mm Hg) and low-density lipoprotein cholesterol (LDL-C, <1.8 mmol/L) at 1 year post myocardial infarction were assessed using logistic regression.

Results

Structure and processes reflecting nurses' autonomy and role in the CR team associated with patients achieving systolic BP and/or LDL-C targets included the following: nurses having treatment algorithms to adjust BP medication (odds ratio [95% confidence interval]: systolic BP, 1.22 [1.05–1.42]; LDL-C, 1.17 [1.03–1.34]) and lipid-lowering medication (systolic BP, 1.14 [1.00–1.29]; LDL-C, 1.17 [1.05–1.30]), patients having the same nurse throughout follow-up (systolic BP, 1.07 [1.03–1.11]; LDL-C, 1.10 [1.06–1.14]), number of follow-up hours with a nurse (systolic BP, 1.13 [1.07–1.19]), having regular case rounds to discuss patient cases during follow-up (LDL-C, 1.22 [1.09–1.35]), and nurses having training in counseling methods (systolic BP, 1.06 [1.03–1.10]).

Conclusion

Components reflecting CR nurses' autonomy and role in the team are of importance for patients attaining risk factor targets post myocardial infarction. The results could provide guidance for optimizing nurses' competence and responsibilities within the CR team to improve patient care.
Barriers to Seeking Healthcare Services After Sexual Assault: A Scoping Review
Authors: Lucea Marguerite B. , Ramirez Andrea , Martino Natalie
Published: June 2024

Background

Sexual violence by an intimate partner or by a stranger remains highly prevalent in the United States. Yet, the use of post-sexual-assault health care is still underutilized. Persons in vulnerable populations such as immigrants, LGBTQIA+, and Black women may experience additional barriers to care.

Objective

We sought to determine the extant research in this area, the methodologies used, and whether specific barriers exist for seeking sexual assault services. We sought to understand if barriers differed for vulnerable populations.

Inclusion Criteria

Peer-reviewed literature published before September 2023, written in English, conducted in the United States, and that included survivors of sexual violence and explored barriers to seeking care postassault (i.e., sexual assault nurse examiners) were included in the review.

Methods

Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews protocols were followed. PubMed, Scopus, CINAHL, PsycINFO, and PTSDpubs databases were used to identify literature that met the inclusion criteria, from which we selected 14 publications.

Results

Much of the literature employed qualitative or mixed methods designs. Several studies focused on underserved minority groups, including immigrant women, Black women, and homeless youth. Common barriers existed on the intrapersonal, interpersonal, organizational, community, and societal levels.

Conclusion

The literature provided substantive context for the multilevel barriers, all contributing to survivors remaining silent rather than seeking much-needed help. Although there is a need for additional research on barriers to sexual assault services specifically, the extant research supports strengthening multilevel, alternative approaches to deliver much-needed services.
Intraoperative fluorescence redefining neurosurgical precision
Authors: Regmi Moksada , Li Yanni , Wang Yingjie , Liu Weihai , Dai Yuwei , Liu Shikun , Ma Ke , Pan Laisan , Gan Jiacheng , Liu Hongyi , Zheng Xiuling , Yang Jun , Wu Jian , Yang Chenlong
Published: June 2024

Surgical resection is essential for treating solid tumors, with success largely dependent on the complete excision of neoplastic cells. However, neurosurgical procedures must delicately balance tumor removal with the preservation of surrounding tissue. Achieving clear margins is particularly challenging in cases like glioblastoma due to the limitations of traditional white light visualization. These limitations often result in incomplete resections, leading to frequent recurrences, or excessive resection that harms vital neural structures, causing iatrogenic nerve damage, which can lead to sensory and functional deficits. Current statistics reveal a 90% recurrence rate for malignant gliomas. Similarly, an 8% incidence of iatrogenic nerve trauma contributes to an estimated 25 million cases of peripheral nerve injury globally each year. These figures underscore the urgent need for improved intraoperative techniques for lesion margin and nerve identification and visualization. Recent advances in neurosurgical imaging, such as fluorescence-guided surgery (FGS), have begun to address these challenges. Fluorescent agents used in FGS illuminate target tissues, although not all do so selectively. Despite the promising results of agents such as 5-aminolevulinic acid and indocyanine green, their applications are mainly limited by issues of sensitivity and specificity. Furthermore, these agents do not effectively address the need for precise nerve visualization. Nerve Peptide 41, a novel systemically administered fluorescent nerve-targeted probe, shows promise in filling this gap. This review assesses the major fluorescent imaging modalities in neurosurgery, highlighting each of their benefits, limitations, and potential.
Technique for Weaning From Peripheral Venopulmonary Extracorporeal Membrane Oxygenation in Combined Cardiopulmonary Failure
Authors: Brewer J. Michael , Maybauer Marc O.
Published: June 2024

Venopulmonary (VP) extracorporeal membrane oxygenation (ECMO) is a mode capable of supporting both pulmonary and right ventricular (RV) functions. Weaning patients from VP ECMO requires careful assessment of both RV and respiratory system recovery, which may occur at different rates. The weaning strategy described herein begins with weaning of respiratory ECMO support, followed by discontinuation of RV support. We also discuss situations in which the standard weaning strategy may require modification.
The Prognostic Significance of Collagen VI in Pancreatic Ductal Adenocarcinoma
Authors: Kesti Ella , Borgmästars Emmy , Hagström Jaana , Mustonen Harri , Seppänen Hanna , Haglund Caj , Sund Malin
Published: June 2024

Objectives

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and lack of biomarkers. A rich desmoplastic tumor stroma is considered a hallmark of PDAC and previous studies have indicated upregulated expression of collagen VI (COL6) in PDAC. COL6 is shown to associate with prognosis in many cancers but has been less extensively studied in PDAC.

Materials and Methods

The expression of COL6 was analyzed by immunohistochemistry in tissue microarrays containing resected tumor tissue samples from PDAC patients (n = 164). Significance of COL6 was estimated with Kaplan-Meier survival estimates and multivariable Cox regression analysis. COL6 protein and mRNA expression patterns were further investigated in publicly available datasets.

Results

There were no statistically significant (P < 0.05) differences in survival when comparing high and low protein expression of any of the analyzed COL6 α-chains (α1(VI): hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.64–1.28; α2(VI): HR 1.28, 95% CI 0.86–1.89; α3(VI): HR 0.91, 95% CI 0.64–1.29). Similar results were obtained when assessing public data from the Cancer Proteome Atlas, Clinical Proteomic Tumor Analysis Consortium, and The Cancer Genome Atlas.

Conclusions

In contrast with previous studies and some other cancers, we did not find any association of COL6 tissue expression and PDAC survival.
DICER1 Mutations Define the Landscape of Poorly Differentiated Thyroid Carcinoma in Children and Young Adults
Authors: Ver Berne Jonas , Van den Bruel Annick , Vermeire Stefanie , De Paepe Pascale
Published: June 2024

Poorly differentiated thyroid carcinoma (PDTC) is a rare malignancy, representing ~1% of all thyroid tumors. It is characterized by high-grade histologic features without the anaplastic characteristics observed in anaplastic thyroid carcinoma. Although rare in children and young adults, there is emerging evidence of clinical and genetic differences with PDTC in adults. We present a case of a 19-year-old female with a right thyroid lobe nodule classified as an EU-TIRADS 5 lesion. Subsequent FNAC showed a cellular aspirate of solitary cells and scant microfollicles with variable nuclear irregularities, which was designated a Bethesda class IV lesion. Thyroidectomy revealed histopathological features consistent with PDTC, including solid/trabecular growth, increased mitotic activity, central necrosis, and extensive vascular invasion. Molecular analysis identified germline and somatic DICER1 mutations in the absence of other established driver mutations of PDTC. This case report describes the fourth reported patient with a PDTC and germline DICER1 mutation. Our findings contribute to a limited body of literature on pediatric/young adult PDTC cases and highlight the pivotal role of DICER1 mutations. Emerging evidence suggests that pediatric PDTC may exhibit unique clinical and genetic characteristics, prompting further research into its molecular profile.
Gingival Hyperplasia Masquerading as Tumor Lesion, Possibly Linked to Amlodipine Use
Authors: Sawamura Hirokazu , Koyasu Sho , Sugimoto Akihiko , Fujimura Shintaro , Nakamoto Yuji
Published: June 2024

A 70-year-old woman under amlodipine treatment for hypertension presented with a hemorrhagic mass in the mandibular gingiva. Imaging studies revealed high signal intensity in T2-weighted MRI and moderate 18F-FDG accumulation at the lesion’s periphery. Although no malignancy was detected, the lesion continuously grew, prompting excision. Histopathological examination confirmed gingival hyperplasia attributed to amlodipine use. Drug-induced gingival hyperplasia typically presents as diffuse swelling; however, this lesion manifested as a polyp, posing diagnostic challenges. Reports on imaging findings for drug-induced gingival hyperplasia are limited. Understanding imaging patterns alongside clinical history aids in accurate diagnosis.
Diagnostic Accuracy of SPECT for Mild Traumatic Brain Injury
Authors: Koziarz Alex , Koziarz Frank , Shen Rui , Gopee-Ramanan Prasaanthan , Black Sandra E. , Worsley Daniel , Chan Ian Y.M. , Streiner David L. , Zukotynski Katherine A.
Published: June 2024

Purpose

This study examines the diagnostic accuracy of brain perfusion SPECT for mild traumatic brain injury (mTBI).

Patients and Methods

A systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO: CRD42023484636). Five databases were searched for studies evaluating brain perfusion SPECT in adult patients with mTBI (GCS 13–15). Study quality was assessed using a modified QUADAS-2 tool. A meta-analysis was performed to pool proportions of hypoperfusion abnormalities across brain lobes.

Results

Of 4735 records, 22 studies (5 longitudinal [40% high quality], 17 cross-sectional [24% high quality]) were included totaling 800 patients (mean age, 37.4 ± 12.6 years; 36.4% female). Meta-analysis of proportions indicated that the frontal lobe most frequently showed hypoperfusion on brain perfusion SPECT (pooled proportion 40.1% [95% confidence interval, 31.2% to 49.8%], 99/254, I
2 = 54.5%), followed by the temporal lobe (26.1% [95% confidence interval, 19.9% to 33.6%], 68/254, I
2 = 30.7%). Several studies found that hypoperfusion abnormalities were associated with neuropsychological findings. Also, brain perfusion SPECT could detect abnormalities not seen on MRI. Abnormalities in perfusion on brain perfusion SPECT may be more readily detected with a quantitative assessment compared with a visual assessment alone, although there appears to be no consensus on the optimal method for image interpretation. Evidence evaluating the sensitivity and specificity of brain perfusion SPECT for mTBI was limited. Using the GRADE framework, the evidence was rated as low.

Conclusions

Although perfusion abnormalities can be seen in patients with mTBI, commonly in the frontal and temporal lobes, the findings are nonspecific and may derive from various factors. Ultimately, brain perfusion SPECT provides additional information for mTBI, but the final added value for the detection of mTBI is unknown.
Pilot Feasibility Study
Authors: Rousseau Caroline , Metz Raphaël , Kerdraon Olivier , Ouldamer Lobna , Boiffard Florence , Renaudeau Karine , Ferrer Ludovic , Vercouillie Johnny , Doutriaux-Dumoulin Isabelle , Mouton Alexis , Le Thiec Maelle , Morel Agnès , Rusu Daniela , Santiago-Ribeiro Maria-Joao , Campion Loïc , Arlicot Nicolas , Kraeber-Bodéré Françoise
Published: June 2024

Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism.

Patients and Methods

Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3H-DPA-714, and 3H-PK-11195 autoradiography were conducted.

Results

The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%–94%). 18F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18F-DPA-714 TACs were identified, categorized as “above muscular,” “equal to muscular,” and “below muscular” with reference to the muscular background. For the “above muscular” group (2 HAB and 2 MAB), “equal muscular” group (3 HAB, 3 MAB, and 1 LAB), and “below muscular” group (1 LAB and 1 MAB), tumor TACs showed a 18F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUVmean of 4.02 (2.09–5.31), 1.66 (0.93–3.07), and 0.61 (0.43–1.02).

Conclusions

This study successfully demonstrated TNBC tumor targeting by 18F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.
Parasite prevalence is determined by infection state- and risk-dependent dispersal of the host
Authors: Baines Celina B. , Shaw Allison K.
Published: June 2024

The spread of parasites and the emergence of disease are currently threatening global biodiversity and human welfare. To address this threat, we need to better understand those factors that determine parasite persistence and prevalence. It is known that dispersal is central to the spatial dynamics of host–parasite systems. Yet past studies have typically assumed that dispersal is a species-level constant, despite a growing body of empirical evidence that dispersal varies with ecological context, including the risk of infection and aspects of host state such as infection status (parasite-dependent dispersal; PDD). Here, we develop a metapopulation model to understand how different forms of PDD shape the prevalence of a directly transmitted parasite. We show that increasing host dispersal rate can increase, decrease or cause a non-monotonic change in regional parasite prevalence, depending on the type of PDD and characteristics of the host–parasite system (transmission rate, virulence, and dispersal mortality). This result contrasts with previous studies with parasite-independent dispersal which concluded that prevalence increases with host dispersal rate. We argue that accounting for host dispersal responses to parasites is necessary for a complete understanding of host–parasite dynamics and for predicting how parasite prevalence will respond to changes such as human alteration of landscape connectivity.

This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
The biotic and abiotic contexts of ecological selection mediate the dominance of distinct dispersal strategies in competitive metacommunities
Authors: Khattar Gabriel , Savary Paul , Peres-Neto Pedro R.
Published: June 2024

While the influence of dispersal on ecological selection is the subject of intense research, we still lack a thorough understanding of how ecological selection operates to favour distinct dispersal strategies in metacommunities. To address this issue, we developed a model framework in which species with distinct quantitative dispersal traits that govern the three stages of dispersal—departure, movement and settlement—compete under different ecological contexts. The model identified three primary dispersal strategies (referred to as nomadic, homebody and habitat-sorting) that consistently dominated metacommunities owing to the interplay of spatiotemporal environmental variation and different types of competitive interactions. We outlined the key characteristics of each strategy and formulated theoretical predictions regarding the abiotic and biotic conditions under which each strategy is more likely to prevail in metacommunities. By presenting our results as relationships between dispersal traits and well-known ecological gradients (e.g. seasonality), we were able to contrast our theoretical findings with previous empirical research. Our model demonstrates how landscape environmental characteristics and competitive interactions at the intra- and interspecific levels can interact to favour distinct multivariate and context-dependent dispersal strategies in metacommunities.

This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning
Authors: Lu Dazhi , Zheng Yan , Hao Jianye , Zeng Xi , Han Lu , Li Zhigang , Jiao Shaoqing , Ai Jianzhong , Peng Jiajie
Published: June 2024

Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal cell carcinoma. However, our understanding of ccRCC risk genes remains limited. This gap in knowledge poses significant challenges to the effective diagnosis and treatment of ccRCC. To address this problem, we propose a deep reinforcement learning-based computational approach named RL-GenRisk to identify ccRCC risk genes. Distinct from traditional supervised models, RL-GenRisk frames the identification of ccRCC risk genes as a Markov decision process, combining the graph convolutional network and Deep Q-Network for risk gene identification. Moreover, a well-designed data-driven reward is proposed for mitigating the lim-itation of scant known risk genes. The evaluation demonstrates that RL-GenRisk outperforms existing methods in ccRCC risk gene identification. Additionally, RL-GenRisk identifies ten novel ccRCC risk genes. We successfully validated epidermal growth factor receptor (EGFR), corroborated through independent datasets and biological experimentation. This approach may also be used for other diseases in the future.
Infralimbic projections to the basal forebrain mediate extinction learning
Authors: Fernandes-Henriques Carolina , Guetta Yuval , Sclar Mia , Zhang Rebecca , Miura Yuka , Friedman Allyson K. , Likhtik Ekaterina
Published: June 2024

Fear extinction learning and retrieval are critical for decreasing fear responses to a stimulus that no longer poses a threat. While it is known that the infralimbic region (IL) of the medial prefrontal cortex mediates retrieval of an extinction memory through projections to the basolateral amygdala (BLA), the contribution of the IL to extinction learning is not well-understood. Given the strong projection from the IL to the basal forebrain (BF), a center of attentional processing, we investigated whether this pathway participates in extinction, and compared it to the IL-BLA pathway. Using retrograde tracing, we first demonstrate that projections from the IL to the BF originate from superficial (L2/3) and deep cortical layers (L5), and that they are denser than IL projections to the BLA. Next, combining retrograde tracing with labeling of the immediate early gene cFos, we show increased activity of the L5 IL-BF pathway during extinction learning and increased activity of the L2/3 IL-BLA pathway during extinction retrieval. Ourin vitrorecordings demonstrate that neurons in the IL-BF pathway become more excitable towards the end of extinction learning, but less excitable during extinction retrieval. Finally, using optogenetics we show that inactivation of the IL-BF pathway impairs extinction learning, leaving retrieval intact. We propose that the IL acts as a switchboard operator during extinction, with increased L5 IL-BF communication during learning and increased L2/3 IL-BLA communication during retrieval. Anxiety and stress-related changes in IL physiology could affect one or multiple lines of communication, impairing different aspects of extinction.

Significance Statement

Extinction of conditioned fear is a widely used behavioral approach to diminish fear, with projections from infralimbic prefrontal cortex to the amygdala known for mediating extinction memory retrieval. However, less is known about infralimbic pathways involved in extinction learning. We use neuroanatomical tracing, behavior, slice recordings, and circuit manipulation to show that infralimbic output to the basal forebrain, an attention processing center, is denser than to the amygdala, and is active during extinction learning rather than retrieval. Neurons in the infralimbic-basal forebrain pathway become more excitable as extinction learning progresses, and then less excitable during extinction retrieval. Moreover, inhibiting this pathway impairs extinction learning. Our findings identify different lines of communication the infralimbic cortex uses for extinction learning and retrieval.
Rare ring conformations in PDB: Facts or wishful thinking?
Authors: Bučeková Gabriela , Doshchenko Viktoriia , Chareshneu Aliaksei , Porubská Jana , Pajtinka Michal , Oleksik Michal , Svoboda Tomáš , Horský Vladimír , Svobodová Radka
Published: June 2024

Protein structural data are highly valuable for research, and many significant results have been published on their basis. A key point for their credibility and applicability is their quality. An important facet of protein structure quality is the validation of ligands. Some aspects of ligand quality have already been validated by established quality metrics. However, validation of ring conformation has yet to be comprehensively performed despite rings strongly influencing the formation of the ligand’s scaffold and shape. Most rings form several conformations that differ in their stability. The most stable ones occur frequently in nature and should, therefore, be found in Protein Data Bank (PDB) structures.

In this article, we examined which conformations of rings occur in PDB structures. Our analysis focused on conformations of all cyclopentane, cyclohexane, and benzene rings in the PDB. Specifically, we examined 123 264 rings of 24 763 distinct ligands, which instances occur in 44 022 protein structures. In general, we found that most of the rings (98.32 %) are in energetically favourable conformations. Surprisingly, the existence of most of the energetically unfavourable ring conformations (2 067 samples, 1.68 %) is not supported by experimental data. Only 291 unfavourable ring conformations (0.24 %) are backed by experimental data that are accurate enough to distinguish the conformation, which shows that the existence of energetically unfavourable ring conformations is rarely supported by structural or experimental evidence.

Our results suggest that each occurrence of untypical ring conformation in the PDB may indicate a potential error and should be carefully analysed.
Reward responses to vicarious feeding depend on BMI
Authors: Järvinen Lili , Santavirta Severi , Putkinen Vesa , Karlsson Henry K. , Seppälä Kerttu , Sun Lihua , Hudson Matthew , Hirvonen Jussi , Nuutila Pirjo , Nummenmaa Lauri
Published: June 2024

Eating is inherently social for humans. Yet, most neuroimaging studies of appetite and food-induced reward have focused on studying brain responses to food intake or viewing pictures of food alone. Here we used functional magnetic resonance imaging (fMRI) to measure haemodynamic responses to “vicarious” feeding. The subjects (n=97) viewed series of short videos representing naturalistic episodes of social eating intermixed with videos without feeding / appetite related content. Viewing the vicarious feeding (versus control) videos activated motor and premotor cortices, thalamus, and dorsolateral prefrontal cortices, consistent with somatomotor and affective engagement. Responses to the feeding videos were also downregulated as a function of the participants’ BMI. Altogether these results suggest that seeing others eating engages the corresponding motor and affective programs in the viewers’ brain, potentially increasing appetite and promoting mutual feeding.
Rab27b promotes lysosomal function and alpha-synuclein clearance in neurons
Authors: Scholz Kasandra , Pattanayak Rudradip , Roschonporn Ekkatine , Pair Frank Sanders , Nobles Amber , Yacoubian Talene A.
Published: June 2024

Alpha-synuclein (αsyn) is the key pathogenic protein implicated in synucleinopathies including Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). In these diseases, αsyn is thought to spread between cells where it accumulates and induces pathology; however, mechanisms that drive its propagation or aggregation are poorly understood. We have previously reported that the small GTPase Rab27b is elevated in human PD and DLB and that it can mediate the autophagic clearance and toxicity of αsyn in a paracrine αsyn cell culture neuronal model. Here, we expanded our previous work and further characterized a role for Rab27b in neuronal lysosomal processing and αsyn clearance. We found that Rab27b KD in this αsyn inducible neuronal model resulted in lysosomal dysfunction and increased αsyn levels in lysosomes. Similar lysosomal proteolytic defects and enzymatic dysfunction were observed in both primary neuronal cultures and brain lysates from Rab27b knockout (KO) mice. αSyn aggregation was exacerbated in Rab27b KO neurons upon treatment with αsyn preformed fibrils. We found no changes in lysosomal counts or lysosomal pH in either model, but we did identify defects in acidic vesicle trafficking in Rab27b KO primary neurons which may drive lysosomal dysfunction and promote αsyn aggregation. Rab27b OE enhanced lysosomal activity and reduced insoluble αsyn accumulation. Finally we found elevated Rab27b levels in human postmortem incidental Lewy Body Disease (iLBD) subjects relative to healthy controls. These data suggest a role for Rab27b in neuronal lysosomal activity and identify it as a potential therapeutic target in synucleinopathies.
An Information Processing Pattern from Robotics Predicts Unknown Properties of the Human Visual System
Authors: Battaje Aravind , Godinez Angelica , Hanning Nina M , Rolfs Martin , Brock Oliver
Published: June 2024

We tested the hypothesis that an algorithmic information processing pattern from robotics, Active InterCONnect (AICON), could serve as a useful representation for exploring human vision. We created AICON-based computational models for two visual illusions: the shape-contingent color aftereffect and silencing by motion. The models reproduced the effects seen in humans and generated surprising and novel predictions that we validated through human psychophysical experiments. Inconsistencies between model predictions and experimental results were resolved through iterative model adjustments. For the shape-contingent color aftereffect, the model predicted and experiments confirmed weaker aftereffects for outline shape manipulations and individual differences in perceived aftereffects. For silencing by motion, the model predicted and experiments validated unexpected trends as well as individual differences. Our findings demonstrate AICON's ability to capture relevant aspects of human visual information processing including variability across individuals. It highlights the potential for novel collaborations between synthetic and biological disciplines.
Divisive attenuation based on noisy sensorimotor predictions accounts for excess variability in self-touch
Authors: Valè Nicola , Tomić Ivan , Gironés Zahara , Wolpert Daniel M , Kilteni Konstantina , Bays Paul M
Published: June 2024

When one part of the body exerts force on another, the resulting tactile sensation is perceived as weaker than when the same force is applied by an external agent. This phenomenon has been studied using a force matching task, in which observers are first exposed to an external force on a passive finger and then instructed to reproduce the sensation by directly pressing on the passive finger with a finger of the other hand: healthy participants consistently exceed the original force level. However, this exaggeration of the target force is not observed if the observer generates the matching force indirectly, by adjusting a joystick or slider that controls the force output of a motor. Here we present the first detailed computational account of the processes leading to exaggeration of target forces in the force matching task, incorporating attenuation of sensory signals based on motor predictions. The model elucidates previously unappreciated contributions of multiple sources of noise, including memory noise, in determining matching force output. We show that the predictive component can be isolated by quantifying attenuation as the discrepancy between direct and indirect self-generated forces, rather than direct versus externally generated forces. Our computational account makes the prediction that attenuated sensations will display greater trial-to-trial variability than unattenuated ones, because they incorporate additional noise from motor prediction. Quantitative model fitting of force matching data based on close to 500 human participants confirmed the prediction of excess variability in self-generated forces and provided evidence for a divisive rather than subtractive mechanism of attenuation, while highlighting its predictive nature.