bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Assessment of Guideline Adherence and Treatment Outcomes From Clostridioides difficile Infection Following the IDSA 2021 Clinical Guideline Update: Clostridioides difficile Infection
Authors: Dubberke Erik R , Li Qinghua , Obi Engels N , Turzhitsky Vladimir , Siddiqui Fakhar , Nathanson Brian H
Published: September 2024

Background

The 2021 update to the Infectious Diseases Society of America Clostridioides difficile infection (CDI) guidelines recommended fidaxomicin as the preferred treatment over vancomycin for patients with initial and recurrent CDI. Few studies have examined how treatment patterns and clinical outcomes of hospitalized CDI patients changed after the postguideline update or contemporary real-world outcomes of fidaxomicin vs vancomycin.

Methods

This retrospective, observational study used the PINC AI Healthcare Database on adult patients who received CDI treatment between 1/2020 and 6/2021 (pre period) and between 10/2021 and 9/2022 (post period). We examined treatment patterns of fidaxomicin, vancomycin, and metronidazole, as well as clinical and health care resource use outcomes of patients treated exclusively with fidaxomicin vs vancomycin, using nearest-neighbor propensity matching and hierarchical regression methods. As a sensitivity analysis, we repeated the fidaxomicin vs vancomycin comparisons among patients with recurrent and nonrecurrent index infections.

Results

A total of 45 049 patients with CDI from 779 US hospitals met initial inclusion criteria. Comparing the pre vs post periods, the proportion of patients treated with fidaxomicin increased from 5.9% to 13.7% (P < .001), vancomycin use decreased from 87.9% to 82.9% (P < .001), and metronidazole use decreased from 21.6% to 17.2% (P < .001). When comparing fidaxomicin vs vancomycin in the post period, fidaxomicin was associated with lower CDI recurrence (6.1% vs 10.2%; P < .001) and higher sustained clinical response (91.7% vs 87.8%; P < .001). Ninety-day postdischarge costs were not significantly different between groups. A sensitivity analyses showed similar findings.

Conclusions

Since the 2021 guideline update, fidaxomicin use has increased significantly but could be further utilized given its association with better clinical outcomes and no increase in postdischarge costs.
The case for Dalit reparations
Authors: Thorat Amit
Published: September 2024

Research on caste to date has examined the largely contemporary situation of the ex-untouchables and descendants of the caste-enslaved in India, the Dalits, and made policy suggestions. This paper builds an argument based on historic origins and the evolution of the caste social structure and on how this longest surviving system of oppression continues to have a severe impact on the lives of the descendants. It not only provides a justification for why reparations are owed to this community and are necessary to bridge the social gap, but also looks at the various forms it could take, as a legislated policy of redress for an historic injustice.
Effects of mixotroph evolution on trophic transfer
Authors: Honig Meredith A , Barbaglia Gina S , Doyle Margaret D , Moeller Holly V
Published: September 2024

Plankton form the foundation of marine food webs, playing fundamental roles in mediating trophic transfer and the movement of organic matter. Increasing ocean temperatures have been documented to drive evolution of plankton, resulting in changes to metabolic traits that can affect trophic transfer. Despite this, there are few direct tests of the effects of such evolution on predator–prey interactions. Here, we used two thermally adapted strains of the marine mixotroph (organism that combines both heterotrophy and autotrophy to obtain energy) Ochromonas as prey and the generalist dinoflagellate predator Oxyrrhis marina to quantify how evolved traits of mixotrophs to hot and cold temperatures affects trophic transfer. Evolution to hot temperatures reduced the overall ingestion rates of both mixotroph strains, consequently weakening predator–prey interactions. We found variability in prey palatability and predator performance with prey thermal adaptation and between strains. Further, we quantified how ambient temperature affects predator grazing on mixotrophs thermally adapted to the same conditions. Increasing ambient temperatures led to increased ingestion rates but declines in clearance rates. Our results for individual, pairwise trophic interactions show how climate change can alter the dynamics of planktonic food webs with implications for carbon cycling in upper ocean ecosystems.
Collaboration, crowdsourcing, and misinformation
Authors: Jia Chenyan , Lee Angela Yuson , Moore Ryan C , Decatur Cid Halsey-Steve , Liu Sunny Xun , Hancock Jeffrey T
Published: September 2024

One of humanity's greatest strengths lies in our ability to collaborate to achieve more than we can alone. Just as collaboration can be an important strength, humankind's inability to detect deception is one of our greatest weaknesses. Recently, our struggles with deception detection have been the subject of scholarly and public attention with the rise and spread of misinformation online, which threatens public health and civic society. Fortunately, prior work indicates that going beyond the individual can ameliorate weaknesses in deception detection by promoting active discussion or by harnessing the “wisdom of crowds.” Can group collaboration similarly enhance our ability to recognize online misinformation? We conducted a lab experiment where participants assessed the veracity of credible news and misinformation on social media either as an actively collaborating group or while working alone. Our results suggest that collaborative groups were more accurate than individuals at detecting false posts, but not more accurate than a majority-based simulated group, suggesting that “wisdom of crowds” is the more efficient method for identifying misinformation. Our findings reorient research and policy from focusing on the individual to approaches that rely on crowdsourcing or potentially on collaboration in addressing the problem of misinformation.
Different sodium concentrations of noncancerous and cancerous prostate tissue seen on MRI using an external coil
Authors: Tan Josephine L , Kalia Vibhuti , Pautler Stephen E , Bauman Glenn , Gast Lena V , Müller Max , Nagel Armin M , Thiessen Jonathan D , Scholl Timothy J , Akbari Alireza
Published: September 2024

Background

Sodium (23Na) MRI of prostate cancer (PCa) is a novel but underdocumented technique conventionally acquired using an endorectal coil. These endorectal coils are associated with challenges (e.g., a nonuniform sensitivity profile, limited prostate coverage, patient discomfort) that could be mitigated with an external 23Na MRI coil.

Purpose

To quantify tissue sodium concentration (TSC) differences within the prostate of participants with PCa and healthy volunteers using an external 23Na MRI radiofrequency coil at 3 T.

Materials and Methods

A prospective study was conducted from January 2022 to June 2024 in healthy volunteers and participants with biopsy-proven PCa. Prostate 23Na MRI was acquired on a 3-T PET/MRI scanner using a custom-built 2-loop (diameter, 18 cm) butterfly surface coil tuned for the 23Na frequency (32.6 MHz). The percent difference in TSC (ΔTSC) between prostate cancer lesions and surrounding noncancerous prostate tissue of the peripheral zone (PZ) and transition zone (TZ) was evaluated using a 1-sample t-test. TSC was compared to apparent diffusion coefficient (ADC) measurements as a clinical reference.

Results

Six healthy volunteers (mean age, 54.5 years ± 12.7) and 20 participants with PCa (mean age, 70.7 years ± 8.3) were evaluated. A total of 31 lesions were detected (21 PZ, 10 TZ) across PCa participants. Compared to noncancerous prostate tissue, prostate cancer lesions had significantly lower TSC (ΔTSC, –14.1% ± 18.2, P = .0002) and ADC (ΔADC, –26.6% ± 18.7, P < .0001).

Conclusion

We used an external 23Na MRI coil for whole-gland comparison of TSC in PCa and noncancerous prostate tissue at 3 T. PCa lesions presented with lower TSC compared to surrounding noncancerous PZ and TZ tissue. These findings demonstrate the feasibility of an external 23Na MRI coil to quantify TSC in the prostate and offer a promising, noninvasive approach to PCa diagnosis and management.
Use of traditional tools and micro-computed tomography for the taxonomy of carnivorous bivalves from the deep waters of Southwestern Atlantic
Authors: Pacheco Leonel I , Teso Valeria , Pastorino Guido
Published: September 2024

In this study, we conduct a morphological integrative analysis, using traditional techniques and micro-computed tomography imaging, on Septibranchia species. Specimens deposited in malacological collections and samples collected aboard the research vessels Puerto Deseado and Austral off Mar del Plata (~36°S), San Jorge Gulf (~46°), and Marine Protected Area Namuncurá/Burdwood Bank area (~54°S), at depths ranging from 200 to 3000 m, are the subjects of this study. Seven species were identified, including Cardiomya cleryana (d’Orbigny, 1846), Cardiomya knudseni (Allen & Morgan, 1981), Lyonsiella cf. fragilis Allen & Turner, 1974, and Cetoconcha spinulosa (Thiele, 1912), previously found in the study area. Cardiomya fragilissima (E. A. Smith, 1885), an Antarctic/sub-Antarctic species, extends its distribution up to 36°S. Two new species, Cetoconcha gigas sp. nov. and Lyonsiella tentaculata sp. nov., are described. A lectotype is designated for Pholadomya adelaidis Hedley, 1916 and a neotype for Sphenia cleryana d’Orbigny, 1846. A detailed description of the morphological characters of each species and genus, along with insights into their geographical and bathymetric distribution, are provided. The micro-computed tomography analysis of Cardiomya cleryana, Cardiomya fragilissima, and Cetoconcha spinulosa contributed to a detailed anatomical inspection and revealed the presence of muscle bundles associated with the anterior portion of the visceral mass in the scanned specimens.
The evolutionary history and biogeographical distribution of the Mesozoic relic genus Chilelimnophila (Diptera, Limoniidae)
Authors: Krzemiński Wiesław , Kania-Kłosok Iwona , Arillo Antonio , Kopeć Katarzyna , Santos Daubian , Soszyńska Agnieszka
Published: September 2024

This study presents novel findings that expand our understanding of the evolutionary history and diversity of the Limoniidae subfamily Limnophilinae, with a specific focus on the relict genus Chilelimnophila. The family Limoniidae is well documented in the fossil record, with many species considered relicts in the modern fauna. Our study is based on the discovery of the first fossil specimens of Chilelimnophila in both Cretaceous Spanish and Kachin amber. The new materials have allowed the establishment of a new subgenus Chilelimnophila (Ribeironia) Krzemiński, Kania-Kłosok et Arillo, subgen. nov. and three new species: Chilelimnophila (Ribeironia) amorimi Krzemiński, Kania-Kłosok et Arillo, sp. nov., Chilelimnophila (Chilelimnophila) wangi Krzemiński, Kania-Kłosok et Arillo, sp. nov., and Chilelimnophila (Chilelimnophila) parva Krzemiński, Kania-Kłosok et Arillo, sp. nov. This research also significantly extends the stratigraphic range of the genus, providing evidence of its existence dating back to the Early Cretaceous period. The morphology and phylogenetic analysis of Chilelimnophila and related genera within the Limoniidae subfamily Limnophilinae provide valuable insights into the evolutionary relationships of these organisms. Furthermore, our research highlights the unique environmental conditions of Cretaceous Spanish and Kachin amber formations, which differ significantly from the current habitat of these organisms.
Exploring the Effects of Trichoderma virens Biofungicide on Carrot Cavity Spot and Soil Fungal Community Dynamics
Authors: Tagele Setu Bazie , Gachomo Emma W.
Published: September 2024

Carrot cavity spot (CCS) has conventionally been managed with fungicides. However, fungicide resistance, their potential risks to human health and the environment, and the increasing demand for organic produce necessitate the exploration of biofungicides as alternatives. In this study, we evaluated varying concentrations of SoilGard (Certis USA, Columbia, MD), a Trichoderma virens-based biofungicide, for efficacy against different CCS-causing Pythium species in vitro. Additionally, its effects on taxonomic and functional diversities of soil fungal communities were studied in vivo in the greenhouse. To our knowledge, this is the first study reporting SoilGard's effectiveness against CCS, with emphasis on its potential as an alternative for fungicide-resistant Pythium isolates. Our in vitro study revealed that SoilGard efficacy was significantly dose-dependent and isolate-specific, thus highlighting the importance of selecting its application rate and the target isolate. Analysis of soil fungal communities using Illumina MiSeq sequencing revealed that SoilGard exerted a significant, albeit temporary, effect on the fungal community structure. It negatively impacted co-occurrence network complexity and alpha diversity in carrot-cultivated soil, whereas bare soil communities remained largely unaffected, thus explaining why preplant applications may yield better results. Our study showed that carrot cultivation without SoilGard enhanced fungal diversity, which was more pronounced late in the season, possibly due to carrot root-associated exudates. Our study sheds light on how complex interactions within soil fungal communities can be impacted by the application of beneficial/pathogenic microbes.
Comparison of Oswestry Disability Index Scores Between Surgical Candidates and General Population
Authors: Bansal Aiyush , Kumar Rakesh , Lipson Patricia , Alostaz Murad , Nemani Venu , Leveque Jean-Christophe , Louie Philip K.
Published: September 2024

Study Design.

A mixed-methods investigation with both retrospective and prospective components.

Objective.

Determine the mean Oswestry Disability Index (ODI) scores for individuals who underwent surgical intervention compared to a non-surgical population and identify threshold values that distinguish between these groups.

Summary of Background Data.

The Oswestry Disability Index (ODI) quantifies disability in patients with low back pain and commonly serves as a significant determinant in lumbar spine pathology and surgical outcomes. An empirically established ODI threshold can aid in optimizing surgical decision-making processes.

Methods.

This study retrospectively analyzed 557 patients who consulted with a spine surgeon and subsequently underwent lumbar spine surgery from 2019 to 2023. Additionally, ODI scores were surveyed from 797 individuals in the general American population using the CloudResearch Connect platform, with participants matched for age and sex according to US census data. Mean ODI scores stratified by age group and sex were calculated for each cohort. Receiver Operating Characteristic (ROC) analysis was utilized to ascertain ODI cutoff values for different demographics.

Results.

The retrospective cohort demonstrated a higher disability level with an overall mean ODI of 34.7 (95% CI [33.1, 36.2]) for ages 18-89. In contrast, the general population surveyed had a mean ODI of 14.4 (95% CI [13.3, 15.4]). An ROC-derived ODI threshold of 16.5 within the comprehensive age group of 18-89 exhibited a sensitivity of 0.84 and a specificity of 0.68.

Conclusion.

The ODI values identified in this study offer benchmarks that can assist in the evaluation process for spine surgery. These findings highlight the importance of considering ODI scores as part of a comprehensive clinical evaluation, rather than as standalone indicators for surgical intervention. Further prospective validation of these findings and their integration into clinical practice is recommended for future research.
In Situ Assembly of Dual Mobility Liners in Isolated Cup Revision in Hip Arthroplasty: A Technical Note
Authors: Bell Louisa , Bühler Tobias , Leunig Michael , Rüdiger Hannes A.
Published: September 2024

Objective:

Isolated cup revisions to a dual mobility system through the minimally invasive direct anterior approach represent a major challenge in revision hip arthroplasty.

Materials and Methods:

We present 2 cases of isolated cup revision to a dual mobility system due to aseptic loosening, in which the dual mobility liners were assembled in situ. In the first case, a well-fixed cemented monobloc stem did not require revision; in the second, the collared prosthetic head could not be removed from the well-fixed stem.

Results:

In situ assembly of the polyethylene liner to the prosthetic head was performed using the standard press, designed for back-table assembly.

Conclusion:

In situ assembly of dual mobility liners is technically simple using standard instruments and can be performed through a direct anterior approach.
Mohs Micrographic Surgery With Melanocytic Immunostains for T1a/b Invasive Melanoma Yields <1% Local Recurrence and Disease-specific Mortality
Authors: Bangalore Kumar Anagha , Trischman Thomas , Asamoah Eucabeth , Todd Austin , Vidal Nahid Y. , Demer Addison M.
Published: September 2024

BACKGROUND

The use of Mohs micrographic surgery with melanocytic immunostains (MMS-I) for cutaneous melanoma is increasing.

OBJECTIVE

To assess local recurrence, melanoma-specific death rates in patients with invasive melanoma treated with MMS-I.

MATERIALS AND METHODS

A single-center retrospective review of patients with invasive melanoma treated with MMS-I from January 2008 to December 2018.

RESULTS

Three hundred fifty-two patients (359 melanomas) were included. The median age was 71 years; most patients were male (252%; 71.6%). Most tumors were T1a/b (341, 95%), H/N (322; 89.7%), and lentigo maligna subtype (281, 78.3%). At a median follow-up of 4.3 years, local recurrence rates were 1.4% (5) and 0.9% (3) among all-stage and T1a/b tumors, respectively. There were 3 melanoma-related deaths (0.9%).

CONCLUSION

MMS-I is associated with <1% risk of local recurrence and disease-specific mortality for T1a/b melanomas.
Antidepressant Medication Use for Treatment of Chronic Ocular Pain
Authors: De Lott Lindsey B. , Khan Noreen , Woodward Maria A. , Clauw Daniel J. , Galor Anat
Published: September 2024

Chronic ocular pain (COP) is a leading cause of eye care visits in the US and has a substantial impact on quality of life and visual functioning. Although many conditions underlie COP, such as dry eye disease or post-herpetic neuralgia, some people experience pain without significant ocular signs on examination or known risk factors (eg, traumatic injury). Antidepressant medications that act primarily on the central nervous system, such as tricyclic antidepressants and serotonin and norepinephrine reuptake inhibitors, are often used to treat patients with COP, but a recent Cochrane review and network meta-analysis investigating 25 different antidepressants concluded that only two serotonin and norepinephrine reuptake inhibitors, have sufficient data to support their use in chronic pain. For all other medications, the evidence was of low certainty. We contend that while these medications are not a cure-all for chronic pain or COP, it is premature to conclude that these medications have no role in their treatment. We provide a rationale for continued use of antidepressant medications as part of a multimodal targeted treatment for patients with COP.
Serum uric acid-lowering effect of sacubitril/valsartan in hypertensive patients: evaluation by switching from angiotensin II receptor blockers
Authors: Horio Takeshi , Iwashima Yoshio , Yoshiyama Minoru , Fukuda Daiju , Hasegawa Takamasa , Fujimoto Kohei
Published: September 2024

Objective

Since hyperuricemia is a risk factor for cardiovascular disease and chronic kidney disease, it is necessary to pay attention to trends in uric acid levels when treating hypertensive patients with drugs. The present study investigated the effect of switching from angiotensin II receptor blocker (ARB) to sacubitril/valsartan on serum uric acid levels in treated hypertensive patients and further examined what factors could be associated with its effect.

Methods

In 75 hypertensive patients under treatment with at least one antihypertensive agent including ARB, clinic blood pressure and biochemical parameters were assessed before and after drug switching to sacubitril/valsartan (200 mg/day).

Results

Clinic SBP and DBP significantly decreased after drug switching to sacubitril/valsartan (P < 0.0001, respectively). Serum creatinine, estimated glomerular filtration rate (eGFR), and urinary protein did not change after switching to sacubitril/valsartan, but serum uric acid significantly decreased (5.70 ± 1.44 to 5.40 ± 1.43 mg/dl, P = 0.0017). The degree of uric acid lowering was greater in patients switching from ARB plus diuretic than in those switching from ARB, but switching to sacubitril/valsartan from ARB only (except losartan) also significantly decreased uric acid levels. In all subjects, the change in serum uric acid after drug switching to sacubitril/valsartan was closely correlated with the change in eGFR (r = −0.5264, P < 0.0001).

Conclusion

Our findings indicate that switching from ARB to sacubitril/valsartan reduces serum uric acid levels in hypertensive patients and suggest that this uric acid-lowering effect may be associated with an increase in eGFR.
Atypical presentation of Kaposi sarcoma in an HIV-negative patient: a case report and comprehensive literature review
Authors: Jebrini Nidal E.M. , Natsheh Motaz A. , Jaber Mohanad , Muhtaseb Rahaf , Qunaibi Yaman , Hidri Haytham , Sarahneh Husein A.
Published: September 2024

Introduction:

Kaposi’s sarcoma (KS) is a systemic disease that is marked by the presence of neoplastic lesions caused by human herpesvirus-8 (HHV-8) infections. KS usually impacts people with weakened immune systems, although there have been a few cases of it occurring in individuals with normal immune function. Medical records and histopathological slides of the case were retrospectively reviewed. This work has been reported based on SCARE criteria.

Case Presentation:

A 51-year-old man from Palestine came in with a single, painless, purple growth on his left forearm that had been growing quickly for 6 months. The patient did not have a history of using immunosuppressants, HIV infection, or engaging in unconventional sexual practices. Histopathological examination confirmed nodular-stage KS, with positive HHV-8 immunostain. The lesion was excised without complications, and the patient remains under periodic follow-up.

Discussion:

KS typically manifests with multiple lesions in individuals with weakened immune systems. This case showcases a unique presentation in a patient with a strong immune system and no notable risk factors. Histopathological confirmation is necessary to differentiate between benign and infectious vascular lesions when considering the diagnosis of KS. The treatment approaches can differ depending on the extent of the lesion and the condition of the patient.

Conclusion:

This case emphasizes the significance of considering KS as a potential cause for solitary vascular lesions, even in people who have a healthy immune system. It also emphasizes the need for a comprehensive diagnostic evaluation and personalized management.
Foix–Alajouanine syndrome: a comprehensive overview of rare but relevant diagnosis
Authors: Atallah Oday , Almealawy Yasser F. , Arian Roua , Dwebi Assma , Badary Amr , Abdul Hussein Abbas F. , Sanker Vivek , Zafarshamspour Saber , Chaurasia Bipin , Agrawal Amit , Pastrana Brandes Santiago , Azab Mohammed A.
Published: September 2024

Introduction:

Foix–Alajouanine syndrome (FAS) is an uncommon neurological disorder marked by the gradual development of spinal cord congestion. First documented by Foix and Alajouanine in 1926. Although it is infrequent, delayed or misdiagnosis is nonetheless prevalent, resulting in inadequate therapy and unfavorable results.

Methods:

Using the PubMed database, MEDLINE, and EMBASE, we collected data on FAS patients and conducted a pooled analysis. The term ‘FAS’ was used to search for related articles. Our search was restricted to previous clinical case reports or series that were published in English. Non-English articles were excluded. We included the articles in the period from 1974 to 2024. Articles were eligible if the radiographic and clinical findings were indicative of FAS. A thorough research analysis was performed, examining case reports that specifically addressed this issue. This study examines the clinical symptoms, difficulties in diagnosis, methods of treatment, and outcomes related to FAS.

Results:

FAS predominantly impacts the elderly population. A total of 26 patients were diagnosed with FAS. The median age of affected individuals was 53 (SD ±15.96). The ratio of males to females is roughly 5:1. The clinical manifestations encompass gradual muscle weakness and sensory impairments. The diagnosis is dependent on radiological evaluations, specifically MRI and digital subtraction angiography. Possible treatments include endovascular therapy, surgical closure of arteriovenous fistula, or a combination of the two. Significant improvements in neurological impairments can be achieved by early intervention.

Conclusion:

The diagnosis of FAS continues to be difficult due to its infrequency and varied clinical manifestations. Prompt and precise diagnosis is essential for proper intervention, typically utilizing endovascular or surgical methods. Additional research is required to determine prognostic markers and enhance long-term care techniques for this rare neurological condition.
Outcomes of laser hemorrhoidoplasty for grade II–IV hemorrhoidal disease in Bangladesh
Authors: Islam Md. Saiful , Shrestha Abhigan B. , Chowdhury Faisal , Ziko Md. R.K.
Published: September 2024

Background:

Laser hemorrhoidoplasty is a minimally invasive procedure to treat hemorrhoids and has shown better outcomes. Less is known about its utility in a lower middle-income country; Bangladesh.

Method:

Between March 2023 and December 2023, 86 patients with grade II–IV hemorrhoids underwent laser hemorroidoplasty. Follow up was assessed on 1st week, 2nd week, and 6th week including pain, satisfaction, symptom improvement, incapacity for work, complications, reduction, and recurrence.

Results:

The study included 86 patients, with a higher proportion of male participants (73.3%) and a mean age of 55.43±13.6 years. The majority of subjects (68.60%) had grade 3 hemorrhoids. The average surgery duration was 14.70±4.70 minutes All individuals experienced substantial decreases in the size of their hemorrhoids (100%) and reported high levels of satisfaction after the operation (97.7%). The use of the Wilcoxon signed-rank test demonstrated a statistically significant reduction in both the Visual Analog Scale (VAS) and Patient Global Impression of Improvement (PGI-I) ratings during the three subsequent observation periods (1st week, 2nd week, and 6th week). The 6th week complication rate was 19.8%. Additional mucopexy was performed on all patients with grade IV and three patients with grade III hemorrhoids.

Conclusion:

Laser hemorroidoplasty is a day-care procedure, that is safe and efficacious and can be used in rural area settings with good patient satisfaction. Mucopexy is required in some cases of large hemorrhoidal mass to prevent recurrence.
Clinical significance of appendicoliths in conservative treatment of acute complicated appendicitis patients with peri-appendiceal abscess: a single-center retrospective study
Authors: Min Lingqiang , Lu Jing , He Hongyong
Published: September 2024

Background:

This study aimed to analyze the clinical data of patients who received conservative treatment for acute complicated appendicitis with peri-appendiceal abscess, identify factors influencing the success rate, and improve treatment strategies.

Methods:

The clinical data of acute complicated appendicitis patients with peri-appendiceal abscess who received conservative treatment at the Department of Emergency Surgery, Zhongshan Hospital, Fudan University, from January 2016 to March 2023, were retrospectively analyzed.

Results:

A total of 80 patients were included in our study. Patients were divided into two groups based on the outcomes of ultrasound-guided drainage: The Drainage group (n=28) and the Antibiotic group (n=52). The baseline characteristics of the two groups were comparable. In the Antibiotic group, the surgery rate was 30.4% for patients with an appendicolith and 6.9% for those without. In the Drainage group, the surgery rate was 33.3% for patients with an appendicolith and 27.3% for those without. The presence of an appendicolith significantly correlated with the need for surgery in the Antibiotic group (P=0.026), but not in the Drainage group (P=0.771). For patients who underwent surgery, the incidence of surgical site infections did not differ significantly (P=0.656), and the median length of postoperative hospital stay was similar between the groups (4.0 days vs. 3.0 days, P=0.337).

Conclusion:

The presence of an appendicolith is a risk factor for the failure of antibiotic therapy alone in acute complicated appendicitis patients with peri-appendiceal abscess. However, it does not affect the surgical rate in those who underwent successful drainage.
A Patient With Cryptococcal Meningitis Accompanied With Acute Intracranial Hypertension Treated by Ventricular Abdominal-wall Drainage
Authors: Yu Le , Mu Cuiping , Lan Xiaolei , Cheng Lei , Li Huanting , Li Zhaojian , Feng Yugong , Cui Zhenwen
Published: September 2024

Intracranial hypertension is considered a common and severe complication of cryptococcal meningitis (CM), contributing to early mortality and neurological sequelae. Timely and effective control of elevated intracranial pressure is crucial for the management of CM. Herein, the authors present a case of ventricular abdominal wall drainage for CM accompanied with acute intracranial hypertension. Notably, the patient has a history of taking immunosuppressants for thoracic and abdominal diffuse lymphangiomatosis. After continuous drainage of cerebrospinal fluid combined with standardized antifungal treatment, the patient recovered well.
Updated clinical evidence and molecular features of antibody-drug conjugates for advanced urothelial carcinoma
Authors: Wang Ching-Yun , Teng Pai-Chi , Hong Jian-Hua
Published: September 2024

Platinum-based chemotherapy and immunotherapy are the primary systemic treatments for patients with advanced urothelial carcinoma (UC). However, the efficacy of these systemic therapies has yet to be optimized. Antibody-drug conjugates (ADCs), which combine the specificity of monoclonal antibodies with the cytotoxic potency of small-molecule drugs, have emerged as a promising new class of targeted therapies for UC. Currently, the Food and Drug Administration has approved 2 ADCs, namely Padcev and Trodelvy, for the treatment of advanced UC. This review provides an overview of the clinical evidence supporting the use of ADCs in patients with UC and summarizes the molecular features underlying these ADCs, which could be essential for understanding resistance mechanisms and minimizing treatment-related adverse events.
Retrospective analysis of Acinetobacter baumannii bacteraemia risk factors, complications and mortality in a tertiary university hospital in Saudi Arabia
Authors: Kaki Reham
Published: September 2024

Introduction. There are many multidrug-resistant isolates of the nosocomial pathogen, Acinetobacter baumannii, causing severe healthcare-acquired infections in terminally ill patients with high mortality and morbidity rates.

Aim. This study aims to retrospectively analyse A. baumannii bacteraemia (ABB) cases in Saudi Arabia, where the information is sparse regarding the prevalence, risk factors, clinical disease, antibiotic regimen, antibiotic susceptibility, treatment outcomes and mortality associated with this infection.

Methods. A retrospective chart review was conducted between 1 January 2015 and 31 December 2022 to identify all patients aged 14 years and above with ABB. Demographic and clinical data, as well as results from laboratory analyses, were collected from patients’ electronic charts. Statistical analyses were performed on the data to identify factors associated with 90-day mortality.

Results. Of the 122 ABB cases, 71 (63.4%) died. The factors that were found to be associated with 90-day mortality were the Charlson Comorbidity Index, Pitt bacteraemia score, quick Sequential Organ Failure Assessment score (P<0.001 for each), hospital ward (P<0.02), short duration of antibiotic treatment (P<0.01) and higher age (P<0.05). The most common source of infection was central line-associated bloodstream infection in 52.7%. Also associated with mortality were inappropriate antimicrobial therapy (P<0.02) and empirical use of colistin (P<0.05). In many patients, ABB was caused by carbapenem-resistant A. baumannii [(CRAB), 69.6%], and 74.4% of those patients died.

Conclusion. To prevent ABB-associated mortality, an appropriate regimen and duration of treatment are necessary. Hospitals should also practice proper hygiene to prevent the spread of ABB. CRAB is a growing threat in hospitals in Saudi Arabia, especially in the critical care setting, and carries a very high risk of mortality.
Nitrosotalea devaniterrae gen. nov., sp. nov. and Nitrosotalea sinensis sp. nov., two acidophilic ammonia oxidising archaea isolated from acidic soil, and proposal of the new order Nitrosotaleales ord. nov. within the class Nitrososphaeria of the phylum Nitrososphaerota
Authors: Lehtovirta-Morley Laura E. , Ge Chaorong , Ross Jenna , Yao Huaiying , Hazard Christina , Gubry-Rangin Cécile , Prosser James I. , Nicol Graeme W.
Published: September 2024

Two obligately acidophilic, mesophilic and aerobic soil ammonia-oxidising archaea were isolated from a pH 4.5 arable sandy loam (UK) and pH 4.7 acidic sulphate paddy soil (PR China) and designated strains Nd1T and Nd2T, respectively. The strains shared more than 99 % 16S rRNA gene sequence identity and their genomes were both less than 2 Mb in length, sharing 79 % average nucleotide identity, 81 % average amino acid identity and a DNA G+C content of approximately 37 mol%. Both strains were chemolithotrophs that fixed carbon dioxide and gained energy by oxidising ammonia to nitrite, with no evidence of mixotrophic growth. Neither strain was capable of using urea as a source of ammonia. Both strains were non-motile in culture, although Nd1T does possess genes encoding flagella components and therefore may be motile under certain conditions. Cells of Nd1T were small angular rods 0.5–1 µm in length and grew at pH 4.2–5.6 and at 20–30 °C. Cells of Nd1T were small angular rods 0.5–1 µm in length and grew at pH 4.0–6.1 and at 20–42 °C. Nd1T and Nd2T are distinct with respect to genomic and physiological features and are assigned as the type strains for the species Nitrosotalea devaniterrae sp. nov. (type strain, Nd1T=NCIMB 15248T=DSM 110862T) and Nitrosotalea sinensis sp. nov. (type strain, Nd2T=NCIMB 15249T=DSM 110863T), respectively, within the genus Nitrosotalea gen. nov. The family Nitrosotaleaceae fam. nov. and order Nitrosotaleales ord. nov. are also proposed officially.
Identification of SLC45A4 as a pain gene encoding a neuronal polyamine transporter
Authors: Middleton Steven J , Markússon Sigurbjörn , Åkerlund Mikael , Deme Justin C. , Tseng Mandy , Li Wenqianglong , Zuberi Sana R , Kuteyi Gabriel , Sarkies Peter , Baskozos Georgios , Perez-Sanchez Jimena , Hébert Harry L , Toikumo Sylvanus , Farah Adham , Maxwell Susan , Dong Yin Y , Kranzler Henry R , Linley John E , Smith Blair H , Lea Susan M. , Parker Joanne L , Lyssenko Valeriya , Newstead Simon , Bennett David L
Published: September 2024

Polyamines are regulatory metabolites with key roles in transcription, translation, cell signalling and autophagy1. They are implicated in multiple neurological disorders including stroke, epilepsy and neurodegeneration and can regulate neuronal excitability through interactions with ion channels2. Polyamines have been linked to pain showing altered levels in human persistent pain states and modulation of pain behaviour in animal models3. However, the systems governing polyamine transport within the nervous system remain unclear. In undertaking a Genome Wide Association Study (GWAS) of chronic pain intensity in the UK-Biobank we found significant association with variants mapping to theSLC45A4gene locus. In the mouse nervous system SLC45A4 expression is enriched in all sensory neuron sub-types within the dorsal root ganglion including nociceptors. Cell-based assays show that SLC45A4 is a selective plasma membrane polyamine transporter, whilst the cryo-EM structure reveals a novel regulatory domain and basis for polyamine recognition. Mice lacking SLC45A4 show normal mechanosensitivity but reduced sensitivity to noxious heat and algogen induced tonic pain that is associated with reduced excitability of peptidergic nociceptors. Our findings thus establish a role for neuronal polyamine transport in pain perception and identify a new target for therapeutic intervention in pain treatment.
Predicting Mobile Health Clinic Utilization for COVID-19 Vaccination in South Carolina: A Statistical Framework for Strategic Resource Allocation
Authors: Gezer Fatih , Howard Kerry A. , Bennett Kevin J. , Litwin Alain H. , Sease Kerry K. , Rennert Lior
Published: September 2024

Background

Mobile health clinics (MHCs) are effective tools for providing health services to disadvantaged populations, especially during health emergencies. However, patient utilization of MHC services varies substantially. Strategies to increase utilization are therefore needed to maximize the effectiveness of MHC services by serving more patients in need. The purpose of this study is to develop a statistical framework to identify and prioritize high-risk communities for delivery of MHCs during health emergencies.

Methods

Prisma Health MHCs delivered COVID-19 vaccines to communities throughout South Carolina between February 20, 2021, and February 17, 2022. In this retrospective study, we use generalized linear mixed effects model and ordinal logistic regression model to identify factors associated with, and predict, MHC utilization for COVID-19 vaccination by census tract.

Results

The MHCs conducted 260 visits to 149 sites and 107 census tracts. The site-level analysis showed that visits to schools (RR=2.17, 95% CI=1.47-3.21), weekend visits (RR=1.38, 95% CI=1.03-1.83), and visits when the resources were limited (term 1: 7.11, 95% CI=4.43-11.43) and (term 2: 2.40, 95% CI=1.76-3.26) were associated with greater MHC utilization for COVID-19 vaccination. MHC placement near existing vaccination centers (RR=0.79, 95% CI=0.68-0.93) and hospitals (RR=0.83, 95% CI=0.71-0.96) decreased utilization. Predictive models identified 1,227 (94.7%) census tracts with more than 250 individuals per MHC visit when vaccine resources were limited. Predictions showed satisfactory accuracy (72.6%). The census tracts with potential of high MHC demand had higher adolescent, 30-44 years old, non-White populations, lower Primary Care Practitioners per 1,000 residents, fewer hospitals, and higher cumulative COVID-19 emergency department visits and deaths (compared to census tracts in the low MHC demand category). After the vaccines became widely available, the demand at MHCs declined.

Conclusion

These study findings can be used to improve MHC allocation by identifying and prioritizing medically underserved communities for strategic delivery of these limited resources.
Deficiency of actin depolymerizing factors ADF/Cfl1 in microglia decreases motility and impairs memory
Authors: Crux Sophie , Roggan Marie Denise , Poll Stefanie , Nebeling Felix C. , Schiweck Juliane , Mittag Manuel , Musacchio Fabrizio , Steffen Julia , Wolff Katharina M. , Baral Andrea , Witke Walter , Gurniak Christine , Bradke Frank , Fuhrmann Martin
Published: September 2024

Microglia are highly motile cells that play a crucial role in the central nervous system in health and disease. Here we show that actin depolymerizing factors ADF and Cofilin1 (Cfl1) are key factors of microglia integrity and function. We found a profound morphological phenotype in absence of ADF and Cfl1 in microglia.In vivotwo-photon imaging of microglia with ADF/Cfl1-KO revealed reduced microglial fine processes motility and impaired microglia migration towards a laser-induced lesion. We found increased accumulation of stabilized F-actin and altered microtubule dynamics in ADF/Cfl1-KO microglia, indicating that ADF/Cfl1 are necessary for microglial cytoskeleton dynamics. Interestingly, microglial ADF/Cfl1-deficiency decreased learning and memory, suggesting that impaired microglial cytoskeleton dynamics affect neuronal functions relevant for cognition. Our results reveal a fundamental role of ADF/Cfl1 in microglia function and underscore the importance of these innate immune cells for higher cognitive functions.
Astrocyte-derived PEA116 increases adult hippocampal neurogenesis and confers stress resilience
Authors: Charline Carron , Frédéric Cassé , Sébastien Sultan , Thomas Larrieu , Kévin Richetin , Jeanne Espourteille , Nicolas Robadey , Marta Vilademunt , Andreas Sagner , Francesco Petrelli , Marlen Knobloch , Ruth Beckervordersandforth , Nicolas Toni
Published: September 2024

In the dentate gyrus of the hippocampus, the neurogenic niche regulates several steps of adult neurogenesis, from the proliferation to the integration of newly formed neurons in the hippocampal network. However, the role of astrocytes in the regulation of adult neural stem cell (aNSC) proliferation is still little described. Here, we found that blocking vesicular release from astrocytes decreased cell proliferation in the dentate gyrus, resulting in impaired adult neurogenesis. Inversely, astrocyte-conditioned medium increased cell proliferation in a vesicular release-dependent manner. We identified PEA116 as a peptide released by astrocytes, that is derived from the c-terminal portion of the PEA15 protein and increased cell proliferation. PEA116 increased ERK2 phosphorylation, decreased the expression of genes involved in aNSC quiescence, resulting in aNSC quiescence exit. The ensuing increase in hippocampal neurogenesis improved resilience to chronic stress. These findings highlight a novel peptide produced by astrocytes that regulates the early steps of adult neurogenesis, with an implication for mood disorders.
Granulysin antimicrobial activity promotes dormancy inMycobacterium tuberculosis
Authors: Schmidiger Sarah , McCaffrey Erin F. , Schmidt Jan M. , Hameed Owais Abdul , Mpina Max , Tumbo Anneth , Mfinanga Elirehema , Haraka Frederick , Hiza Hellen , Sasamalo Mohamed , Hella Jerry , Walch Michael , Fellay Jacques , Gagneux Sébastien , Reither Klaus , Carballido José M. , Arbués Ainhoa , Portevin Damien
Published: September 2024

Human tuberculosis (TB) caused byMycobacterium tuberculosis(Mtb) remains a global public health threat. Granulomas constitute a hallmark of TB pathogenesis that can clear, contain or exacerbate an infection. Containment is exploited byMtbas a hideout to persist in a dormant, antibiotic-tolerant state only to resuscitate upon immunosuppression. The immune determinants of a granulomatous response drivingMtbpersistence remain elusive. We here combined anex vivogranuloma model with peripheral blood mononuclear cell (PBMC) specimens from TB patients and a high-dimensional mass cytometry (CyTOF) approach to shed light on the immune factors promptingMtbdormancy. Compared to healthy controls, patient-derivedex vivogranulomas rapidly forceMtbto adopt a dormant-like state; an observation that correlates with the presence of activated innate (-like) cytotoxic lymphocytes. We further demonstrate thatMtbdormancy is induced by direct exposure to granulysin, thereby unravelling an immune escape mechanism to cytotoxic lymphocyte activity.
Identification of a novel basal body-localized epsilon-tubulin inLeishmania
Authors: Seth Arunava , Das Anubhab , Datta Rupak
Published: September 2024

Epsilon-tubulins are unconventional isoforms of the tubulin family, found in only a few organisms so far. We identified a novel epsilon-tubulin inLeishmania major(Lme-tubulin) that exhibits significant sequence similarity and conservation of functional domains with its known counterparts. Lme-tubulin was found to be constitutively expressed in both the extracellular promastigote form of the parasite and the amastigotes residing within infected macrophages. For localization studies, we generated aLeishmaniastrain expressing mNeonGreen-tagged Lme-tubulin using CRISPR-Cas9-mediated endogenous protein tagging method. Imaging studies with this strain revealed Lme-tubulin to be localized near the kinetoplast and at the flagellar base, indicating a basal body localization. That Lme-tubulin is indeed localized at the basal body and not a part of the microtubular network was confirmed when its localization was found to remain unaltered upon treatment with nocodazole, a microtubule disruptor. This is the first experimental finding of an e-tubulin not only in the genusLeishmaniabut in the entireTrypanosomatidaefamily and is likely to incite further research to uncover the physiological role of this intriguing tubulin in this group of protozoan parasites.

Summary Statement

We report for the first time an epsilon-tubulin inLeishmaniaparasite. This nocodazole-insensitive unconventional tubulin is expressed constitutively and found to be localized in the basal body.
Reusable Microfluidic Chambers for Single-Molecule Microscopy
Authors: Alfehaid Janan , Kodikara Sineth G. , Alhajri Tuqa , Kabir Mohammad Lutful , Balci Hamza
Published: September 2024

Maintaining a consistent environment in single molecule microfluidic chambers containing surface-bound molecules requires laborious cleaning and surface passivation procedures. Despite such efforts, variations in non-specific binding and background signals commonly occur across different chambers. Being able to reuse the chambers without degrading the surface promises significant practical and fundamental advantages; however, this necessitates removing the molecules attached to the surface, such as DNA, proteins, lipids or nanoparticles. Biotin-streptavidin attachment is widely used for such attachments as biotin can be readily incorporated to these molecules. In this study, we present single-molecule fluorescence experiments that demonstrate effective resetting and recycling of the chambers at least 10 times using photocleavable biotin (PC-biotin) and UV light exposure. This method differs from alternatives as it does not utilize any harsh chemical treatment of the surface. We show that all bound molecules (utilizing various PC-biotin attachment chemistries) can be removed from the surface by a 5-min UV exposure of a specific wavelength. Non-optimal wavelengths and light sources showed varying degrees of effectiveness. Our approach does not result in any detectable degradation of surface quality, as assessed by non-specific binding of fluorescently labeled DNA and protein samples, and recovery of DNA secondary structure and protein activity. The speed and efficiency of the resetting process, the cost-effectiveness of the procedure, and the widespread use of biotin-streptavidin attachment make this approach adaptable for a wide range of single-molecule applications.