bluuebunny/crossref_metadata_2025 huggingface dataset:
The long-term outcome of chronic thromboembolic pulmonary hypertension: Pulmonary endarterectomy and balloon pulmonary angioplasty
Authors: Yang Kuo-Ming , Wang Mei-Tzu , Tao Chi-Wei , Wu Yih-Jer , Hsu Chih-Hsin , Liao Wei-Chih , Hsu Hsao-Hsun , Lin Meng-Chih , Tsai Fu-Ting , Fu Yun-Ju , Kuo Feng-Yu , Cheng Chin-Chang , Hung Cheng-Chung , Wang Hao-Chien , Yu Chong-Jen , Huang Wei-Chun
Published: January 2024

Background:

The long-term outcome on patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been ideal after standard medical treatment. However, good outcome for patients with CTEPH after interventions such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) has been reported recently. The aim of this study was to evaluate the impact of PEA or BPA on long-term outcomes for CTEPH patients in Han-Chinese population.

Methods:

This was a multicenter, prospective case-control study. Patients with CTEPH were enrolled between January, 2018 and March, 2020. They were divided into two groups, including intervention (PEA or BPA) and conservative groups. The followed-up period was 26 months after treatment. The endpoints were all-cause mortality and CTEPH mortality.

Results:

A total of 129 patients were enrolled and assigned to receive PEA/BPA (N = 73), or conservative therapy (N = 56). Overall, the 26-month survival rate of all-cause mortality was significantly higher in intervention group compared to that in conservative group (95.89% vs 80.36%; log-rank p = 0.0164). The similar trend was observed in the 26-month survival rate of CTEPH mortality (97.26% vs 85.71%; log-rank p = 0.0355). Regarding Cox proportional-hazard regression analysis, the hazard ratios (HRs) on patients with CTEPH receiving intervention in the outcome of all-cause mortality and CTEPH mortality were statistically significant (HR = 0.07 and p = 0.0141 in all-cause mortality; HR = 0.11 and p = 0.0461 in CTEPH mortality).

Conclusion:

This multicenter prospective case-control study demonstrated that intervention such as PEA and BPA increased the long-term survival rate for patient with CTEPH significantly. Intervention was an independent factor in long-term outcome for patients with CTEPH, including all-cause mortality and CTEPH mortality.
Adenocarcinoma In Situ of the Uterine Cervix (AIS) Treated by Loop Electrosurgical Excision Procedure Strategy: An Observational Study
Authors: Soegaard-Andersen Erik , Frandsen Anna Poulsgaard , Sandahl Preben
Published: January 2024

Objectives

Evaluation of the results of treatment of adenocarcinoma in situ by loop electrosurgical excision procedure and the safety of a conservative strategy.

Methods

Identification of all cases of adenocarcinoma in situ treated by loop electrosurgical excision procedure at our institution and follow-up by a conservative strategy. Completeness of the identification of all cases was secured by data from the National Pathology Registry. The treatment strategy was based on cytologic follow-up performed by a general practitioner and, irrespective of margin status of the cone, only the results of the postoperative surveillance were indicative of further treatment.

Results

A total of 224 patients were identified. The overall recurrence rate with a mean follow-up time of 87.8 months was 7.6% (17/224). The recurrence rate in patients with involved margins was significantly higher than in patients with uninvolved margins, 15.7% vs 5.2%, respectively. Six recurrences were diagnosed at first examination 6 months postconization in patients with involved margins. They were treated with hysterectomy in 4 cases and reconization in 1 case. If involvement of margins alone had been an indication of further therapy (hysterectomy or reconization) immediately after conization, the conservative management strategy prevented 46 surgical procedures. Two cases of invasive cancer were diagnosed during follow-up, 150 months and 196 months after primary treatment, and after normal follow-up examinations. These 2 cases must be considered de novo cases and cannot be considered treatment failures.

Conclusion

The conservative management strategy thus seems safe, and unnecessary surgical procedures were avoided.
Late presentation for hepatitis C treatment: prevalence and risk factors in the Swiss Hepatitis C Cohort
Authors: Brunner Nathalie , Grischott Thomas , Bruggmann Philip ,   the Swiss Hepatitis C Cohort Study Group
Published: January 2024

Objective

Patients with ‘late presentation’ (LP) of chronic hepatitis C infection (HCV) have already developed advanced liver disease before receiving direct-acting antiviral (DAA) treatment. Even after successful treatment, the risk of morbidity and premature death remains elevated, leading to an unnecessary disease burden. This study aimed to assess the prevalence of LP within the prospective observational Swiss Hepatitis C Cohort (SCCS) and evaluate risk factors as determinants of LP.

Methods

Treatment-naïve participants of SCCS who received DAA treatment between 2014 and 2019 were included. Demographic, clinical and behavioural data were compared between the LP and non-LP strata. LP prevalence was calculated over time and by year. LASSO regression was used to identify potential risk factors for LP, and odds ratios were calculated by refitting logistic regression models.

Results

In this explorative, retrospective case–control study using data of n = 5829 SCCS members, a total of 21.3% received their first HCV treatment. The cumulative LP prevalence decreased from mid-2015 and stabilised at 46.5% (n = 579) by the end of 2019. Male gender, higher age and a history of alcohol overuse were associated with a higher risk of LP.

Conclusion

Despite the study’s limitations, LP prevalence was higher than anticipated, considering Switzerland’s availability period and universal access to DAAs. Therefore, any HCV LP should be viewed as a healthcare system failure, primarily in high-income economies. As LP is directly linked to the disease burden, it must be included as a mandatory parameter in surveillance response systems of HCV elimination programs.
Ventilation-perfusion scan for diagnosing pulmonary embolism: do chest x-rays matter?
Authors: Conrad Thomas J. , Lau Han X. , Yerkovich Stephanie T. , Alghamry Alaa , Lee Joseph C.
Published: January 2024

Background

Ventilation-perfusion (V/Q) scan coupled with single photon emission computed tomography (SPECT) is commonly used for the diagnosis of pulmonary embolism (PE). An abnormal chest x-ray (CXR) is deemed to hinder the interpretation of V/Q scan and therefore a normal CXR is recommended prior to V/Q scan.

Aims

To determine if an abnormal CXR impacted on V/Q scan interpretation and subsequent management.

Methods

A retrospective cohort analysis of all patients who underwent a V/Q scan for diagnosis of suspected acute PE between March 2016 and 2022 was performed. CXR reports were reviewed and classified as normal or abnormal. Low-dose computerised tomography was routinely performed in patients above the age of 70. Data regarding V/Q scan results and subsequent management including initiation of anticoagulation for PE or further diagnostic investigations were collected.

Results

A total of 340 cases were evaluated. Of the positive V/Q scans (92/340), 98.3% of the normal CXR were anticoagulated compared to 100% of the abnormal CXR group. Of the negative V/Q scans (239/340), no cases were started on anticoagulation and no further investigations were performed across both normal and abnormal CXR groups. Indeterminate results occurred in only 9 cases with no significant difference in management between normal and abnormal CXR groups.

Conclusion

An abnormal CXR does not affect the reliability of V/Q scan interpretation in the diagnosis of PE when coupled with SPECT. Unless clinically indicated, the mandate by clinical society guidelines for a normal CXR prior to V/Q should be revisited.
Using VARSKIN+v1.2 to estimate dose from direct skin contamination with radionuclides 223Ra, 212Pb and 225Ac; considerations for Nuclear Medicine staff and associated Personal Protective Equipment (PPE)
Authors: Thomson William H.
Published: January 2024

Objective

To calculate depth-weighted doses for 223Ra, 212Pb and 225Ac for the skin sites of trunk, arms/legs, face, wrist, back of hand, fingertip, back and side of fingers using VARSKIN+v1.2.

Methods

Published depth distribution histograms of the basal cells were used with dose averaging in VARSKIN+v1.2. A density correction factor was applied for the 1 g/cc within VARSKIN. Results were compared to the regulatory 70 µm depth and to average depth values for the skin sites.

Results

223Ra has no alpha component at the regulatory 70 µm. This dose is exceeded by the depth-weighted dose rates for all sites (except the fingertip) with factors ×74 (back of finger) to x3600 (trunk). 212Pb and 225Ac have alpha contributions at 70 µm. . For 212Pb, this dose value is greater by over ×2 than the depth-weighted dose rate for the wrist, back of hand, and finger sites, and underestimates dose rates for the other sites. For 225Ac, the 70µm dose rate is exceeded by the depth-weighted dose rates for the trunk, face, arms/legs by factors of ×4–10. Using fixed depth values, the depth-weighted dose rates are larger for all sites except the fingertip. The skin dose is also calculated for biological half-lives of 1, 3 and 6 h. Using the depth-weighted dose rates and a 3 h biological half-life, the activity for 500 mSv is in the range 9–177 Bq for the trunk, face, arms/legs, wrist and hand for all three radionuclides.

Conclusion

For alpha-emitting radionuclides a depth-weighted calculation gives more representative dose values. The very low activity values for 500 mSv skin dose to be exceeded have implications for appropriate staff PPE and training.
In-vivo correlations of fluorescent or radioisotope glucose-analogs in imaging cancer metabolism
Authors: Lin Hongchang , Kobayashi Mariko , Kushiro Keiichiro , Yanagie Hironobu , Shimazoe Kenji , Takahashi Hiroyuki
Published: January 2024

Objective

To investigate the impact of different tracer modifications on the imaging of cancer metabolism, focusing on the comparison of fluorescent glucose-analog tracers (2-NBDG and 2-DG-750) and the radiolabeled tracer 18F-FDG in both in-vitro and in-vivo settings.

Methods

We conducted an in-vitro comparative study using four cancer cell lines, each with unique glucose uptake characteristics. The study involved direct comparison of three tracers: 2-NBDG, 2-DG-750 and 18F-FDG, examining their internalization behaviors, metabolic functionality and localization effects in cancer metabolism imaging.

Results

The study revealed that each tracer exhibits distinct internalization behaviors correlated with imaging label size and type. 18F-FDG showed the highest uptake efficiency. Fluorescent molecules were found to accumulate in tumors primarily due to hydrophobic interactions and possible aggregation, indicating inefficiency in metabolism and suitability for imaging metabolic phenomena when compared to radiolabeled biomolecules.

Conclusion

Our findings demonstrate that despite certain impracticalities, nuclear imaging, particularly using radiolabeled biomolecules like 18F-FDG, offers significant potential for accurately capturing biological phenomena. This is crucial for future advancements in both clinical and research settings. The study emphasizes the limitations of fluorescent molecules in imaging metabolic activities due to their inefficient metabolism and aggregation tendencies.
Intrathecal baclofen for the management of hereditary spastic paraparesis: a systematic review
Authors: Viana Pinto Luisa , Romeiro Isabel , Gouveia Filipa , Ramalho Joana , Ribeiro Silva Sara , Táboas Simões Maria Inês , Rodrigues Leal Joana
Published: January 2024

This systematic review aims to evaluate the use of intrathecal baclofen (ITB) for hereditary spastic paraparesis (HSP) treatment. An extensive search in two electronical databases was performed. We identified articles published between 1990 and 2022 (PubMed, Scopus), and applied the following inclusion criteria: diagnosis of HSP at the time of the intervention, either familial or sporadic; report on the effect of ITB in patients with HSP; test trial via either bolus injections or continuous infusion tests; and ITB pump implantation. A data extraction sheet based on the Cochrane Consumers and Communication Review Group’s data extraction template was created and adapted to collect relevant data. A qualitative analysis was performed to present the results in narrative summary fashion. A total of 6 studies met our inclusion criteria. 51 patients with HSP had a pre-implantation ITB trial. The time since the diagnosis until the pump implantation ranged from 5 to 30 years. The initial bolus ranged from 20 to 50 μg and the mean doses used at steady state ranged from 65 to 705 μg. An improvement in spasticity was observed on the modified Ashworth Scale in patients treated with ITB. Although all studies reported a subjective gait improvement, not all found an objective improvement in gait. The most common side effect reported was catheter-related problems. The findings of this review support the use of ITB as an effective and a viable option for the treatment of spasticity in HSP refractory to conservative therapies.
SDOH and Immigration Status
Authors: Baker Michelle , Campagna Vivian , Mitchell Ellen
Published: January 2024

Purpose:

Social determinants of health (SDOH), the environmental, economic, and social factors that influence people's health outcomes, are widely recognized across health and human services. In addition, there are other factors that can exacerbate SDOH; among them is immigration status. Its influence is so profound that it has been suggested that immigration be considered an SDOH in and of itself (National Academies of Sciences, Engineering, and Medicine, 2018). Across the continuum, case managers need to be aware of the immigration status of their clients (the individuals for whom they advocate and provide services). This is particularly important when addressing the care needs and discharge plans for clients in acute care, community-based health, and workers' compensation. With workers' compensation, when an individual is undocumented and severely injured, immigration status directly impacts the services they may receive under state mandates. Moreover, such limitations can present ethical dilemmas for case managers, including what happens to workers if they are returned to their home countries.

Primary Practice Settings:

SDOH and immigration status can impact individuals in acute care, subacute care, community-based care, and workers' compensation.

Implications for Case Management Practice:

SDOH and immigration status highlight the disparities that exist within health and human services. Although equity is a core value of case management practice, the case manager's ability to provide equal access to care and resources can be severely limited because of the individual's immigration status. At all times, case managers must practice within their licensure and certifications. By recognizing that immigration status should be an SDOH, case management professionals and health and human services organizations can elevate the discussion of how to care for individuals with catastrophic injuries and illnesses who are undocumented.
The Loneliness Epidemic
Authors: Powell Suzanne K.
Published: January 2024

According to the U.S. Surgeon General's Advisory on the Healing Effects of Social Connection and Community, social disconnection is being called a critical public health issue. The epidemic of loneliness is widespread and may have profound consequences for our individual and collective health and well-being. And the “costs” of loneliness are real.
Correlation Between Risk Factors, Degree of Vascular Restenosis, and Inflammatory Factors After Interventional Treatment for Stroke
Authors: Hao Liang , Gao Mingming , Guo Wei , Yao Zhigang
Published: January 2024

Objective:

To study the correlation between risk factors, degree of vascular restenosis, and inflammatory factors after interventional treatment for stroke.

Methods:

The clinical data of 96 stroke patients who received interventional therapy in our hospital from April 2020 to June 2021 were selected for retrospective study, and the postoperative follow-up was 1 year. Univariate and multivariate regression were used to analyze identified factors associated with interventional stroke efficacy. At the same time, the value of inflammatory factor levels in predicting vascular restenosis after interventional stroke was analyzed.

Results:

According to our findings, several risk factors, including body mass index ≥ 25.51 kg/m2, smoking, drinking, hypertension, and diabetes, were identified as contributors to poor postoperative efficacy following stroke intervention (P<0.05). Furthermore, a notable association was observed between the severity of vascular stenosis (P<0.001) and the levels of interleukin 6, interleukin 2, TNF-α, and C-reactive protein. The combined assessment of these serum inflammatory factors exhibited excellent predictive capability for postoperative vascular restenosis and stenosis severity, yielding a sensitivity of 84.30%, a specificity of 81.20%, and an area under the curve of 0.882.

Conclusions:

Obesity, smoking, alcohol consumption, hypertension, and diabetes have been found to be associated with suboptimal outcomes following interventional treatment for stroke. The assessment of preoperative levels of inflammatory factors holds promise in predicting the likelihood of postoperative restenosis to a certain degree.
Association Between Insulin Resistance Markers and Poor Prognosis in Patients With Acute Ischemic Stroke After Intravenous Thrombolysis
Authors: Liu Haimei , Liu Denglu , Zuo Peng
Published: January 2024

Objectives:

This study aims to investigate the significance of insulin resistance markers in predicting poor prognosis in acute ischemic stroke (AIS) patients after intravenous thrombolysis and to establish the corresponding nomogram.

Methods:

From January 2019 to March 2023, the data of 412 patients with AIS who received intravenous alteplase thrombolytic therapy in the Affiliated Taizhou People’s Hospital of Nanjing Medical University were selected. Patients were randomly divided into training groups (70%, 288 cases) and validation groups (30%, 124 cases). In the training group, multivariate logistic regression analysis was used to establish the best nomogram prediction model. The predictive ability of the nomogram was further evaluated by the area under the receiver operating characteristic curve, calibration curve, decision curve analysis, and reclassification analysis. Furthermore, the model was further validated in the validation set.

Results:

Multivariate logistic regression analysis showed that systolic blood pressure, diabetes, National Institutes of Health Stroke Scale score, triglyceride-glucose index, triglyceride-glucose-body mass index, ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol were associated with poor prognosis in AIS patients after intravenous thrombolysis (P<0.05). Compared with conventional factors, the nomogram showed stronger prognostic ability, area under receiver operating characteristic curves were 0.948 (95% CI: 0.920-0.976, P<0.001) and 0.798 (95% CI: 0.747-0.849, P<0.001), respectively.

Conclusions:

Triglyceride-glucose index, triglyceride-glucose-body mass index, and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol levels upon admission can serve as markers for poor prognosis in AIS patients after intravenous thrombolysis. The nomogram enables a more accurate prediction of poor prognosis in AIS patients after intravenous thrombolysis.
Mandibular Gorham-Stout Disease With Implanted Fibular Resorption
Authors: Miao Cheng , Cao Yubin , Li Chunjie
Published: January 2024

Gorham-Stout disease is an extremely rare disease characterized by progressive massive osteolysis with different clinical manifestations. The pathology is characterized by vascular proliferation, leading to destruction and resorption of the bone matrix, but the exact etiology is unknown. It can occur in any part of the body, with few reports of cases involving the maxillofacial region. Herein, the authors report a case of Gorham-Stout disease of the mandible, which started by affecting the alveolar bone and progressed to the mandibular marginal branches and even to the implanted vascularized free fibula.
Decreased Tip Projection and Tip Stiffness Due to A Calcified Septal Extension Graft
Authors: Lee Sae Bin , Min Hyun Jin
Published: January 2024

A septal extension graft is frequently applied in esthetic rhinoplasty in Asia. Autologous cartilage is usually selected for the graft material, and nasal septal cartilage is the most commonly used in septal extension grafts. Although the complication rate is reported to be very low, the authors recently encountered a patient who complained of decreased nasal tip projection and stiffness of the nasal tip. The patient had previously undergone a rhinoplasty, including dorsal augmentation with silicone implant and septal extension graft with septal cartilage. Based on the images, the authors hypothesized that the septal extension graft was calcified, and the intraoperative findings confirmed severe calcification of the previously inserted septal cartilage graft. Herein, the authors report the case of a patient with decreased tip projection and stiffness due to calcification of a previous septal extension graft that used septal cartilage and share the lessons the authors learned from this case.
Orbital Solitary Fibrous Tumors: A 20-Year Cases Series Study in a Single Center
Authors: Zhao Hong-shu , Shi Ji-tong
Published: January 2024

Purpose:

To investigate the clinical manifestations, imaging, pathology, and prognosis of orbital solitary fibrous tumors (OSFTs). In addition, the surgical incisions and the treatment outcomes were also evaluated.

Methods:

A total of 89 patients with pathologically confirmed primary OSFTs were enrolled onto this study. Clinical and histopathological characteristics, imaging data, treatment modalities, and follow-up time, including tumor recurrence and death, were documented. The outcome measures included overall survival and disease-free survival time.

Results:

Among 89 eligible cases, the median age of presentation was 39 years (range: 5–80 years) at the initial diagnosis. The most common presenting symptom was painless proptosis (54, 60.67%), then palpable mass (31, 34.83%), swelling (29, 32.58%), and impaired ocular motility (27, 30.34%). Tumor-related severe impaired vision was found in 11 patients (12.36%), including no-light-perception blindness (6, 6.74%), light-perception (2, 2.25%), and hand-movement (1, 1.12%). The preoperative imaging (computed tomography and magnetic resonance imaging) accurate diagnostic rate of OSFTs was 17.98% (16, 95% CI: 0.098–0.261), and misdiagnosis rate was 25.84% (23, 95% CI: 0.166–0.351). Grossly intact masses were excised for 27 patients (30.34%). Among the 89 patients, 33 (37.08%) were recurrences, and the median of these recurrent patients’ interval between the first and the last operation was 7.33 years (range: 0.12–29.69 years). In 81 patients with complete follow-up data, the median course of the disease was 9.64 years (range: 1.55–33.65 years) from the onset OSFT. The overall survival rate of the 81 patients was 93.83% with a median course of 8.48 years (range: 0.38–30.4 years) from diagnosis of OSFT, and the disease-free survival rate of 81 patients was 91.36% with a median follow-up of 4.76 years (range: 0.08–19.22 years) after the last surgery. Of all the 81 patients, 5 patients (6.17%) developed local recurrence, and 3 patients (3.70%) died from tumor-related diseases, including pulmonary metastasis (2, 2.47%) and complications from intracranial lesions (1, 1.23%). Ten patients (11.24%) received postoperational radiation therapy, including 125I seeds implantation (5, 6.17%) and external beam radiotherapy (5, 6.17%), and remained no recurrence.

Conclusions:

In this series, OSFTs showed long courses and easy recurrence. Although it was very important to choose a proper surgical incision for intact resection of OSFTs at the initial surgery to avoiding recurrence, preoperative imaging is of very limited use since it is not able to identify OSFTs effectively. Postoperative radiotherapy may be beneficial to reduce the recurrence of OSFTs with malignant pathologic features.
The Maxillary Artery Loops Dangerously Approaching the Mandible’s Lingula and Inferior Orbital Fissure
Authors: Rusu Mugurel Constantin , Dumitru Cătălin Constantin , Vrapciu Alexandra Diana
Published: January 2024

The maxillary artery (MA) leaves from the external carotid artery and further courses through the infratemporal fossa to reach the pterygopalatine fossa. It typically has an ascending course either on the lateral or on the medial side of the inferior bundle of the lateral pterygoid muscle. While studying retrospectively, the computed tomography angiogram of an adult male case with peculiar tortuosities of the MA was documented. The left MA described a large inferior sagittal loop applied on the mandible’s ramus’s inner cortical in the pterygomandibular space’s upper part. That loop reached 1.66 cm inferior to the mandible’s notch and 0.5 cm superior to the mandibular foramen and was applied on the mandible’s lingula (spine of Spix). That MA continued to the pterygomaxillary suture, and a second superior coronal loop was found applied on the posterior wall of the maxillary sinus, reaching the inferior orbital fissure. It is therefore mandatory to take good care in the decortication of the mandibular ramus or during osteotomies of the ramus. When an inferior loop of the MA approaches the spine of Spix, bleeding when an inferior alveolar nerve block is performed seems hardly avoidable.
Draft genomes announcement of Vietnamese Xanthomonas euvesicatoria strains causing bacterial spot on pepper
Authors: Subedi Aastha , Nga Nguyen Thi Thu , Tien Doan Thi Kieu , Minsavage Gerald V. , Roberts Pamela D. , Goss Erica M. , Jones Jeffrey B.
Published: January 2024

Xanthomonas euvesicatoria

the primary causal agent of bacterial spot of pepper (BSP), poses a significant global challenge, resulting in severe defoliation and yield losses for pepper growers. We present the whole genome sequences of eight

X. euvesicatoria

strains associated with BSP in Vietnam. These genomes contribute to representation of pepper production regions in the global sample of

X. euvesicatoria

genomes, enabling the development of precise global disease management strategies.
Infrared gas analysis as a method of measuring seagrass photosynthetic rate in the face of desiccation stress
Authors: Capistrant-Fossa Kyle A , Dunton Kenneth H
Published: January 2024

Photosynthesis, a core autotrophic metabolic process for aquatic and terrestrial organisms, is the backbone of the global carbon biogeochemical cycle. Inorganic assimilation of carbon in photosynthesis is relative difficult to measure in an aqueous medium since carbon readily reacts with ions in water. Therefore, aquatic photosynthesis is often measured using secondary methods that introduce uncertainty into measurements (e.g., oxygen evolution). One technique, infrared gas analysis (IRGA), uses a closed gas loop to calculate an accurate carbon budget. Multiple studies have successfully used IRGA with intertidal seagrasses, but it remains unknown how applicable the technology is for underwater plants. Here, we evaluate the potential of IRGA to mea-sure carbon assimilation of subtidal seagrasses temporarily removed from seawater, and evaluate how carbon fixation rates and chlorophyll fluorescence characteristics of subtidal seagrasses change as they desiccate. We use IRGA for four common seagrass species from the Western Gulf of Mexico (Halophila engelmannii, Halodule wrightii, Syringodium filiforme, andThalassia testudinum) paired with pulse amplitude modulated fluorometry to measure desiccation stress.Halophilahad the highest maximum carbon assimilation rate (6.06µmol C m−2s−1), followed byThalassia(5.58µmol C m−2s−1),Halodule(4.75µmol C m−2s−1), andSyringodium(3.63µmol C m−2s−1).Thalassiawas most resistant to desiccation stress as reflected by the plant’s ability to maintain high maximum leaf quantum efficiency (Fv/Fm) while the other species were not. Additionally,Thalassiahad a slower desiccation rate (2.3% min−1cm−2) than 4.79%Syringodium filiforme(4.79% min−1cm−2) andHalodule wrightii(30.17% min−1cm−2). Together, our provide reasonable measures of carbon assimilation and support previous studies of seagrass desiccation stress gradients along depth. Overall, we recognize IRGA as a promising direction for future studies of seagrass productivity and recommend further investigation.
Bayesian Estimation of CooccurrenceAffinitywith Dyadic Regression
Authors: Newbury Arthur
Published: January 2024

Estimating underlying cooccurrence relationships between pairs of species has long been a challenging task in ecology as the extent to which species actually cooccur is partially dependent on their prevalences. While recent work has taken large steps towards solving this problem, the next question is how to assess the factors that influence cooccurrence. Here I show that a recently proposed cooccurrence metric can be improved upon by assigning Bayesian priors to the latent cooccurrence relationships being estimated. In the context of analysing the factors that affect cooccurrence relationships, I demonstrate the need for a generalised linear model (GLM) that takes cooccurrences and species prevalences (not cooccurrence metrics) as its data. Finally, I show the form that such a GLM should take in order to perform Bayesian inference while accounting for non-independence of dyadic matrix data (e.g. distance and cooccurrence matrices).
Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease
Authors: Ladakis Dimitrios C. , Harrison Kimystian L. , Smith Matthew D. , Solem Krista , Gadani Sachin , Jank Larissa , Hwang Soonmyung , Farhadi Farzaneh , Dewey Blake E. , Fitzgerald Kathryn C. , Sotirchos Elias S. , Saidha Shiv , Calabresi Peter A. , Bhargava Pavan
Published: January 2024

Background

Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.

Methods

Global metabolomics was performed in an observational cohort of people with MS followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial, was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2g daily) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory and gut microbiome parameters.

Results

In the observational cohort, higher primary bile acid levels at baseline predicted slower whole brain, brain substructure and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not significantly differ between arms (p=0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4+ and Th1/17 cells decreased, while CD4+ naïve cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted in the TUDCA arm compared to placebo.

Conclusion

Bile acid metabolism in MS is linked with brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.

Trial registration

ClinicalTrials.govNCT03423121

Funding

National MS Society grant RG-1707-28601 to PB, R01 NS082347 from NINDS to PAC and National MS Society grant RG-1606-08768 to SS.

Abstract Figure
Czech Republic butterfly barcoding reveals that distribution of genetic lineages depends on species traits
Authors: Sucháčková Bartoňová Alena , Škopek Patrik , Konvička Martin , Beneš Jiří , Spitzer Lukáš , Sbaraglia Claudio , Vrabec Vladimír , Papp Marešová Jana , Konvičková Hana , Faltýnek Fric Zdeněk
Published: January 2024

Aim

The distribution of within-species lineages has been affected by Quaternary climate changes, and population differentiation has been influenced by species life histories. We investigated whether the distribution of individual mitochondrial genetic lineages reflects the constituent species’ traits. Using the functionally diverse group of butterflies, we examined which lineages are present in Central Europe, an important suture zone.

Location

Czech Republic and Western Palearctic.

Taxon

A total of 140 butterfly species.

Methods

We sequenced DNA barcodes (cytochrome c oxidase 1) (959 sequences) of the entire Czech Republic butterfly fauna and used BOLD data to visualize the species’ biogeographic patterns across Europe. We categorised the distribution patterns of lineages inhabiting the Czech Republic, and used multivariate statistics to interpret these categories by the butterflies’ habitats, life histories, and threat levels.

Results

Open habitat dwellers with specialist traits belonged to Eastern, Southern, and temperate lineages. Habitat generalists and woodland dwellers belonged to the Western lineage, formed several lineages, or displayed low genetic diversity; they often developed on woody plants, were large-winged, and had long flight periods. The most threatened species were the specialists of Southern, Eastern, and temperate lineages.

Main conclusions

The distribution of lineages in Central Europe reflects the history of Quaternary ecosystems: during cold periods of the Pleistocene, the diverse open habitats prevailed, and species could expand westwards. Such species also suffer the most under the current anthropogenic habitat alteration. On the other hand, the mobile generalists and woodland dwellers expanded to Central Europe during the Holocene. Our approach of linking the distribution of lineages with species traits can be transferred to other study systems, and we show that DNA barcoding of under-sampled areas represents a powerful tool for discovering the driving forces of biogeography.
A One Health approach metagenomic study on the antimicrobial resistance traits of canine saliva
Authors: Tóth Adrienn Gréta , Tóth Darinka Lilla , Remport Laura , Tóth Imre , Németh Tibor , Dubecz Attila , Patai Árpád V. , Makrai László , Solymosi Norbert
Published: January 2024

According to the One Health concept, physical proximity among pets and their owners facilitates the spread of various bacteria. Interspecies bacterial transfer media include canine saliva that can be transmitted by licking and biting. Antimicrobial resistance genes (ARGs) are the natural constituents of the bacterial genome. However, human activity can increase the prominence of ARGs. To assess factors that may affect the resistome of the canine oral cavity, the shotgun metagenomic sequencing dataset of 1830 canine saliva samples was bioinformatically analyzed and supplemented with survey results of the physical and behavioral traits of the dogs. Bacteriome and resistome associated with the canine saliva samples were described throughout the analysis. Moreover, the subset of higher public health ARGs and ESKAPE pathogen-related (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) higher public health ARGs were also collected. Further on, the set and subsets of ARGs were studied considering the surveyed traits of the sampled dogs. Overall, 318 ARG types reached sufficiently high detection rates. These ARGs can affect 31 antibiotic drug classes by various resistance mechanisms. ARGs against tetracyclines and cephalosporins appeared in the highest number of samples. However, surprisingly, another CIA group, peptides were represented by ARGs in the third-highest number of samples. Considering further ARG appearance rates in the samples, Critically Important Antimicrobials (CIAs, WHO), such as aminoglycosides, fluoroquinolones, or macrolides, were among the most frequently affected drug classes by higher public health risk ARGs and ESKAPE pathogen related higher public health risk ARGs. Bacteria in the saliva of white and diluted (merle, gray) color dogs and dogs characterized with decreased activity and decreased aggression more often harbored ARGs. Reduced playfulness could have been specifically associated with higher public health risk ARG presence. Even though the oral microbiome of the owners is unknown, One Health and public health implications of the close human-pet bonds and factors potentially underlying the rise in salivary ARG numbers should be considered, mostly in the light of the presence of ARGs affecting critically important drugs for human medicine.
Integrative genomic analysis identifies unique immune environments associated with immunotherapy response in diffuse large B cell lymphoma
Authors: Tumuluru Sravya , Godfrey James K. , Cooper Alan , Yu Jovian , Chen Xiufen , MacNabb Brendan W. , Venkataraman Girish , Zha Yuanyuan , Pelzer Benedikt , Song Joo , Duns Gerben , Sworder Brian J. , Bolen Christopher , Penuel Elicia , Postovalova Ekaterina , Kotlov Nikita , Bagaev Aleksander , Fowler Nathan , Smith Sonali M. , Alizadeh Ash A. , Steidl Christian , Kline Justin
Published: January 2024

Most diffuse large B-cell lymphoma (DLBCL) patients treated with bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was employed to characterize DLBCL immune environments, which effectively segregated DLBCLs into four quadrants – termed DLBCL-immune quadrants (IQ) - defined by cell-of-origin and immune-related gene set expression scores. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute to orchestrating unique DLBCL immune environments. In relapsed/refractory DLBCL patients, DLBCL-IQ assignment correlated significantly with clinical benefit with the CD20 x CD3 BsAb, mosunetuzumab, but not with CD19-directed CAR T cells. DLBCL-IQ provides a new framework to conceptualize the DLBCL immune landscape and uncovers the differential impact of the endogenous immune environment on outcomes to BsAb and CAR T cell treatment.
Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas
Authors: Nair Nishanth Ulhas , Schäffer Alejandro A. , Gertz E. Michael , Cheng Kuoyuan , Zerbib Johanna , Sahu Avinash Das , Leor Gil , Shulman Eldad D. , Aldape Kenneth D. , Ben-David Uri , Ruppin Eytan
Published: January 2024

The co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers, a phenomenon that has been investigated without resolution since the late 1980s. Expanding beyond previous gene-centric studies, we investigate the co-occurrence in a genome-wide manner taking an evolutionary perspective. First, by mining large tumor aneuploidy data, we predict that the more likely order is 10 loss followed by 7 gain. Second, by analyzing extensive genomic and transcriptomic data from both patients and cell lines, we find that this co-occurrence can be explained by functional rescue interactions that are highly enriched on 7, which can possibly compensate for any detrimental consequences arising from the loss of 10. Finally, by analyzing transcriptomic data from normal, non-cancerous, human brain tissues, we provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.
Takakiapossesses a key marker of embryophyte sporopollenin
Authors: Suh Dae-Yeon , Sraan Damanpreet K , Ashton Neil W
Published: January 2024

The enigmatic moss,Takakia lepidozioides, possesses a particular type III polyketide synthase, ASCL (Anther-Specific Chalcone synthase-Like), that is an identifying marker for genuine sporopollenin in the walls of embryophyte spores and pollen grains. By contrast, a survey of all algae with sequenced genomes confirms that they do not possess ASCL and, therefore, their spore walls are not composed of sporopollenin.
Genome-Wide Association Insights into the Genomic Regions Controlling Oil Production Traits inAcrocomia aculeata(neotropical native palm)
Authors: Couto Evellyn Giselly de Oliveira , Morales-Marroquín Jonathan , Alves-Pereira Alessandro , Fernandes Samuel B. , Colombo Carlos Augusto , Adelino de Azevedo Filho Joaquim , Carvalho Cassia Regina Limonta , Zucchi Maria Imaculada
Published: January 2024

Macauba (Acrocomia aculeata) is a non-domesticated neotropical palm that has been attracting attention for economical use due to its great potential for oil production comparable to the commercially used oil palm (Elaeis guineenses). The discovery of associations between quantitative trait loci and economically important traits represents an advance toward macauba domestication. Pursuing this advance, this study performs single-trait and multi-trait GWAS models to identify candidate genes related to oil production traits in macauba. We randomly selected 201 palms from a natural population and analysed 13 traits related to fruit production, processing, and oil content. Genotyping was performed following the genotyping-by- sequencing protocol. SNP calling was performed using three strategies since macauba doesn’t have a reference genome: using i) de novo pipeline, ii)Elaeis guineensesJacq. reference genome, and iii) transcriptome ofAcrocomia aculeata. Single-trait analysis was fitted using five models from GAPIT, while multi-trait analysis was fitted using a multivariate stepwise method implemented in the software TASSEL. Multi-trait analyses were conducted in all pairwise trait combinations. Results showed statistically significant differences in all phenotypic traits studied, and heritability values ranged from 0.63 to 0.95. Gene annotation detected 15 candidate genes in seven traits in the single-trait GWAS and four candidate genes in 10 trait combinations in the multi-trait GWAS. We provide new insights on genomic regions that mapped candidate genes involved in macauba oil production phenotypes. Associated markers to the traits of interest may be valuable resources for the development of marker-assisted selection in macauba for both domestication and pre-breeding purposes.
JAK/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome
Authors: Hargarten Jessica C. , Ssebambulidde Kenneth , Anjum Seher H. , Vaughan Malcolm J. , Xu Jintao , Song Brian , Ganguly Anutosh , Park Yoon-dong , Scott Terri , Hammoud Dima A. , Olszewski Michal A. , Williamson Peter R.
Published: January 2024

Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull’s rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. JAK/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44hiCD62loCD4+effector CD4+T-cells and MHC II+inflammatory myeloid cells, and weight gains in mice, the latter after treatment with antifungals. Based on these data, pathway-driven steroid-sparing human treatment for steroid-refractory PIIRS was initiated using short courses of the JAK/STAT inhibitor ruxolitinib. These were well tolerated and reduced activated HLA-DR+CD4+and CD8+cells and inflammatory monocytes as well as improved brain imaging. Together, these findings support the role of JAK/STAT in PIIRS as well as further study of JAK/STAT inhibitors as potential adjunctive therapy for PIRS and other neural inflammatory syndromes.
Monitoring Report: GLP-1 RA Prescribing Trends - September 2024 Data
Authors: Gratzl Samuel , Rodriguez Patricia J , Cartwright Brianna M Goodwin , Baker Charlotte , Stucky Nicholas L
Published: January 2024

Background

Limited recent data exist on prescribing patterns and patient characteristics for glucagon-like peptide 1 receptor agonists (GLP-1 RAs), an important drug class used as anti-diabetic medication (ADM) for patients with type 2 diabetes mellitus (T2D) and/or anti-obesity medication (AOM) in patients with overweight or obesity.

For brevity, we use the term GLP-1 RA to refer to both GLP-1 RA and dual GLP-1 RA/GIP medications.

Objective

To describe recent trends in prescribing and dispensing of GLP-1-based medications in the US.

Methods

Using a subset of real-world electronic health record (EHR) data from Truveta, a growing collective of health systems that provide more than 18% of all daily clinical care in the US, we identified people who were prescribed a GLP-1-based medication between January 01, 2018 and September 30, 2024. We describe prescribing volumes and patient characteristics over time, by medication, and by FDA-labeled use. Among the subset of patients for whom post-prescription dispensing data is available, we describe the proportion and characteristics of patients who were and were not dispensed a GLP-1 RA following their prescription.

Results

1,449,442 patients were prescribed a GLP-1 RA between January 2018 and September 2024, with 6,341,367 total prescriptions during this period. Among first-time prescriptions for which use could be established, ADMs accounted for 80.3% and AOMs accounted for 19.7%. The most common first-time medication was semaglutide (n = 821,890). Among those with available data, 69.5% of first-time ADM prescriptions overall and 70.6% in June 2024 had a fill within 60 days. By comparison, 45.4% of first-time AOM prescriptions overall and 50.1% in June 2024 had a fill within 60 days.