bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use
Authors: Gilada Trupti , Schnittman Samuel R , White Edward , Mercader Jacqueline , Wang Yixin , Dasgupta Sayan , Valdez Rogelio , Pinto-Santini Delia , Pasalar Siavash , Sanchez Jorge , Gonzales Pedro , Lama Javier R , Bender Ignacio Rachel , Duerr Ann 
Published: March 2022

AbstractBackgroundPrimary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes.MethodsWe studied plasma immune activation biomarkers, viral load, and CD4+ and CD8+ cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks.ResultsCompared to participants enrolled &gt;30 days after HIV acquisition, participants enrolled during acute infection (≤30 days) had higher mean interferon (IFN)–γ and IFN-α2a (1.7-fold and 3.8-fold interquartile range [IQR] higher, respectively). Participants enrolled &gt;30 days after HIV acquisition had higher mean baseline CD8+ cell count (2.7 times the IQR). Alcohol use (positive phosphatidylethanol level) was associated with elevated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70), and smoking was associated with higher macrophage inflammatory protein 1α, TNF-α, and IL-12p70. Most biomarkers declined more quickly in participants who initiated ART immediately; however, substance use and duration of HIV infection at enrollment had little influence on rate of decline.ConclusionsIFN-γ and other biomarkers are elevated during early primary infection, when exposure to HIV antigens is high. Immune activation decreased most quickly in those who started ART during acute/early primary infection. Higher CD8+ cell counts and a trend toward higher soluble CD163 levels during the 30 days after acquisition suggest the onset of compensatory responses and immune exhaustion.
Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Staphylococcus aureus Endocarditis
Authors: Gilbertie Jessica , Ulloa Erlinda R , Daiker Jennifer C , Nguyen Khanh , Smelter Dan , Rose Warren , Geriak Matthew , Schnabel Lauren V , Nizet Victor , Sakoulas George 
Published: March 2022

Abstract

Background
Besides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including infective endocarditis (IE).

Methods
MSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model.

Results
The median duration of bacteremia experienced by patients (n = 12) while on CZ or NAF was 4 days (range 1–16 days) compared with 1 day (range 1–3 days) for patients (n = 5) treated with ETP + CZ (P = .01, Mann-Whitney U test). Cefazolin and NAF alone or in combination did not achieve biofilm eradication at clinically relevant concentrations. However, the addition of ETP to CZ led to bactericidal eradication within biofilms at standard dosing.

Conclusions
Ertapenem reduces CZ concentrations required to eradicate MSSA biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis. Larger studies are needed to investigate ETP plus CZ therapy in the treatment of biofilm-related MSSA infections such as endocarditis.
Lenvatinib for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer: Treatment Optimization for Maximum Clinical Benefit
Authors: Wirth Lori J , Durante Cosimo , Topliss Duncan J , Winquist Eric , Robenshtok Eyal , Iwasaki Hiroyuki , Luster Markus , Elisei Rossella , Leboulleux Sophie , Tahara Makoto 
Published: March 2022

Abstract

Background
Lenvatinib is a multitargeted tyrosine kinase inhibitor approved for treating patients with locally recurrent or metastatic progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC). In this review, we discuss recent developments in the optimization of RR-DTC treatment with lenvatinib.

Summary
Initiation of lenvatinib treatment before a worsening of Eastern Cooperative Oncology Group performance status and elevated neutrophil-to-lymphocyte ratio could benefit patients with progressive RR-DTC. The median duration of response with lenvatinib was inversely correlated with a smaller tumor burden, and prognosis was significantly worse in patients with a high tumor burden. An 18 mg/day starting dose of lenvatinib was not noninferior to 24 mg/day and had a comparable safety profile. Timely management of adverse events is crucial, as patients with shorter dose interruptions benefitted more from lenvatinib treatment. Caution should be exercised when initiating lenvatinib in patients who have tumor infiltration into the trachea or other organs, or certain histological subtypes of DTC, as these are risk factors for fistula formation or organ perforation. The Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT) eligibility criteria should be considered prior to initiating lenvatinib treatment.

Conclusions
Current evidence indicates that patients benefit most from lenvatinib treatment that is initiated earlier in advanced disease when the disease burden is low. A starting dose of lenvatinib 24 mg/day, with dose modifications as required, yields better outcomes as compared to 18 mg/day. Appropriate supportive care, including timely identification of adverse events, is essential to manage toxicities associated with lenvatinib, avoid longer dose interruptions, and maximize efficacy.
Daratumumab Improves Depth of Response and Progression-free Survival in Transplant-ineligible, High-risk, Newly Diagnosed Multiple Myeloma
Authors: Jakubowiak Andrzej J , Kumar Shaji , Medhekar Rohan , Pei Huiling , Lefebvre Patrick , Kaila Shuchita , He Jianming , Lafeuille Marie-Hélène , Cortoos Annelore , Londhe Anil , Mavros Panagiotis , Lin Thomas S , Usmani Saad Z 
Published: March 2022

Abstract

Background
Patients with high-risk, newly diagnosed multiple myeloma (HR-NDMM) who are ineligible for autologous stem cell transplant (ASCT) have limited first-line treatment options. Recent meta-analyses evaluating the impact of incorporating daratumumab in the backbone regimen on progression-free survival (PFS) have found mixed results in these patients.

Materials and Methods
A pooled analysis of patient-level data for ASCT-ineligible patients with HR-NDMM [ie, del(17p), t(4;14), t(14;16)] from the MAIA and ALCYONE trials; stratified by study identifier and adjusting for cytogenetic abnormality subtype, baseline performance status, International Staging System stage, myeloma type, and renal impairment; was conducted. Impact of daratumumab on PFS and rates of complete response or better (≥CR), minimal residual disease (MRD)-negative CR, very good partial response or better (≥VGPR), and overall response (ORR) was compared to control.

Results
Among 101 patients in the daratumumab and 89 patients in the control cohort, median follow-up was 43.7 months. Daratumumab reduced the risk of progression or death by 41% (adjusted hazard ratio for PFS [95% confidence interval (CI)] = 0.59 [0.41-0.85]) versus control. At 36 months, the estimated proportion of patients who did not progress and were still alive was 41.3% in the daratumumab and 19.9% in the control cohort. Rates of ≥CR (41.6% vs. 22.5%), MRD-negative CR (24.8% vs. 5.6%), ≥VGPR (75.2% vs. 46.1%), and ORR (92.1% vs. 74.2%) were higher for daratumumab versus control.

Conclusion
These findings demonstrate that incorporation of daratumumab in frontline treatment regimens reduced the risk of progression or death and improved response rates among ASCT-ineligible HR-NDMM patients.
Systemic Therapies Following Progression on First-line CDK4/6-inhibitor Treatment: Analysis of Real-world Data
Authors: Martin James M , Handorf Elizabeth A , Montero Alberto J , Goldstein Lori J 
Published: March 2022

Abstract

Background
Metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor-2 negative (Her2−) breast cancer remains a significant cause of cancer-related mortality. First-line treatment with endocrine therapy (ET) with a cyclin-dependent kinases 4 and 6 inhibitor (CDK4/6i) has largely become the standard systemic therapy. Following progression, no prospective randomized data exist to help guide second-line treatment.

Materials and Methods
This study used a nationwide electronic health record (EHR)-derived de-identified database, specifically analyzing 1210 patients with HR+/Her2− metastatic breast cancer (MBC) who were treated in the first-line setting with a CDK4/6i from the years 2015-2020. The aim of this study was to assess what therapies were given after first-line progression on CDK4/6i and to observe treatment patterns over time. Determination of second-line treatment efficacy, specifically assessing real-world progression-free survival (rwPFS) and overall survival (OS) was performed.

Results
A total of 839 patients received a documented second-line therapy after progression on first-line CDK4/6i treatment. Chemotherapy was chosen for 29.7% of patients, and the use of chemotherapy decreased over time. Three hundred two (36.0%) of patients continued a CDK4/6i. Data were adjusted for age, race, Eastern Cooperative Oncology Group (ECOG) performance status, stage at breast cancer diagnosis, and insurance payer type. Continuation of the CDK4/6i was associated with improved rwPFS (HR 0.48, 95% CI 0.43-0.53, P &lt; .0001) and OS (HR 0.30, 95% CI 0.26-0.35, P &lt; .0001) compared to chemotherapy. A majority of these patients continued the same CDK4/6i in the second-line setting, as was given in the first-line setting.

Conclusion
While prospective data are needed, analysis of real-world data suggests a survival benefit for continuation of a CDK4/6i beyond frontline progression for patients with HR+/Her2− MBC.
A linear programming-based strategy to save pipette tips in automated DNA assembly
Authors: Sechkar Kirill , Tuza Zoltan A , Stan Guy-Bart 
Published: March 2022

Abstract
Laboratory automation and mathematical optimization are key to improving the efficiency of synthetic biology research. While there are algorithms optimizing the construct designs and synthesis strategies for DNA assembly, the optimization of how DNA assembly reaction mixes are prepared remains largely unexplored. Here, we focus on reducing the pipette tip consumption of a liquid-handling robot as it delivers DNA parts across a multi-well plate where several constructs are being assembled in parallel. We propose a linear programming formulation of this problem based on the capacitated vehicle routing problem, as well as an algorithm which applies a linear programming solver to our formulation, hence providing a strategy to prepare a given set of DNA assembly mixes using fewer pipette tips. The algorithm performed well in randomly generated and real-life scenarios concerning several modular DNA assembly standards, proving to be capable of reducing the pipette tip consumption by up to $59\%$ in large-scale cases. Combining automatic process optimization and robotic liquid handling, our strategy promises to greatly improve the efficiency of DNA assembly, either used alone or combined with other algorithmic DNA assembly optimization methods.
Graphical Abstract
Clinical Features of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 in Indonesia
Authors: Putri Nina Dwi , Prawira Yogi , Tartila Tartila , Jasin Madeleine Ramdhani , Puspitasari Henny Adriani , Puspaningtyas Niken Wahyu , Indawati Wahyuni , Karyanti Mulya Rahma , Setyanto Darmawan Budi , Prayitno Ari , Yuniar Irene , Alatas Fatima Safira , Hidayati Eka Laksmi , Muhaimin Riski , Prawitasari Titis , Soebadi Amanda , Muktiarti Dina , Primacakti Fitri , Rahmadhany Anisa , Octavius Gilbert Sterling , Djer Mulyadi M , Hendarto Aryono , Dewi Rismala , Kaswandani Nastiti , Pudjiadi Antonius Hocky 
Published: March 2022

Abstract

Background
While the number of cases of multisystem inflammatory syndrome in children (MIS-C) is increasing, reported cases in Asian countries are still low, particularly in Indonesia. This study aimed to describe the characteristics of patients with MIS-C in a tertiary referral hospital in Indonesia.

Methods
This is a cross-sectional study with collected data of patients with MIS-C admitted to Dr. Cipto Mangunkusumo from March 2020 to April 2021.

Results
The first case of MIS-C was detected 5 months after the first reported coronavirus disease 2019 case in Indonesia. Thirteen patients out of 158 positive admitted patients for COVID-19 were diagnosed with MIS-C during the study period. Of these 13 patients, 2 patients (15%) had a fatal outcome. Subjects were predominantly male, and the median age was 7.58 years (IQR 12.3) years. Most patients required mechanical ventilation (7 out of 13 patients) and intubation (8 out of 13 patients). Patients who needed intubation usually needed mechanical ventilation. All inflammatory markers, white blood cells, neutrophil counts, and all coagulation factor parameters (except for normal prothrombin time and activated partial prothrombin time) were elevated. The median time to MIS-C diagnosis was 2 days in the survivor group (n = 11) compared to 8.5 days in the non-survivor group (n = 2). Compared to the non-survivor group, those who survived spent more days in the hospital, received vasopressors earlier, and did not require mechanical ventilation as early as the non-survivors.

Conclusions
Our work highlights the differences in MIS-C clinical course, treatment, and clinical outcomes between the two groups.
Trends in Pediatric Hospitalizations and Mortality during the COVID-19 Pandemic in an Urban Setting in Cameroon
Authors: Chiabi Andreas , Forgwei Mfie Nji , Bissong Marie , Niba Loveline , Abah Jevis Ning , Nsame Denis 
Published: March 2022

Abstract

Background
The first case of coronavirus disease 2019 (COVID-19) in Cameroon was recorded in March 2020. In response to the pandemic, most countries like Cameroon instituted a number of control measures to curb its spread accross the country. These COVID-19 control measures added to the fear of this disease within the population may have led to other detrimental health effects like: the pattern of hospitalizations and hospital outcomes.

Methods
We did a cross-sectional study with data from in-patient admission records of children admitted to the pediatric ward of the Regional Hospital Bamenda over a 24 months period (1st of March 2019 to the 28th of February 2021). The pre-pandemic period in Cameroon (that is, the first 12 months, from March 2019 to February 2020) and the pandemic period (that is, the last 12 months, from March 2020 to February 2021) were compared.

Results
A total of 2282 hospitalization records were included in the study. Most of the hospitalized children were males (57.23%). There was a 19.03% decline in pediatric hospitalizations during the first 12 months of the pandemic, which was statistically significant (p = 0.00024). The causes of hospitalizations and mortality remained similar over both periods, with severe malaria, the leading cause of admissions. Hospital deaths before and during the pandemic were 1.6% and 1.9%, respectively.

Conclusion
There was a statistically significant decline in pediatric hospitalizations during the first 12 months of the pandemic as compared to the same period before the pandemic. Hospital mortality and causes of hospitalizations remained similar over both the periods.
Salt- and Osmo-Responsive Sensor Histidine Kinases Activate the Bradyrhizobium diazoefficiens General Stress Response to Initiate Functional Symbiosis
Authors: Wülser Janine , Ernst Chantal , Vetsch Dominik , Emmenegger Barbara , Michel Anja , Lutz Stefanie , Ahrens Christian H. , Vorholt Julia A. , Ledermann Raphael , Fischer Hans-Martin 
Published: March 2022

The general stress response (GSR) enables bacteria to sense and overcome a variety of environmental stresses. In alphaproteobacteria, stress-perceiving histidine kinases of the HWE and HisKA_2 families trigger a signaling cascade that leads to phosphorylation of the response regulator PhyR and, consequently, to activation of the GSR σ factor σEcfG. In the nitrogen-fixing bacterium Bradyrhizobium diazoefficiens, PhyR and σEcfG are crucial for tolerance against a variety of stresses under free-living conditions and also for efficient infection of its symbiotic host soybean. However, the molecular players involved in stress perception and activation of the GSR remained largely unknown. In this work, we first showed that a mutant variant of PhyR where the conserved phosphorylatable aspartate residue D194 was replaced by alanine (PhyRD194A) failed to complement the ΔphyR mutant in symbiosis, confirming that PhyR acts as a response regulator. To identify the PhyR-activating kinases in the nitrogen-fixing symbiont, we constructed in-frame deletion mutants lacking single, distinct combinations, or all of the 11 predicted HWE and HisKA_2 kinases, which we named HRXXN histidine kinases HhkA through HhkK. Phenotypic analysis of the mutants and complemented derivatives identified two functionally redundant kinases, HhkA and HhkE, that are required for nodulation competitiveness and during initiation of symbiosis. Using σEcfG-activity reporter strains, we further showed that both HhkA and HhkE activate the GSR in free-living cells exposed to salt and hyperosmotic stress. In conclusion, our data suggest that HhkA and HhkE trigger GSR activation in response to osmotically stressful conditions which B. diazoefficiens encounters during soybean host infection. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Secondary Analysis of Walking Activities During the Acute Stroke Hospital Stay and Cerebrovascular Health
Authors: Whitaker Alicen A. , Henry Madison L. , Morton Allegra , Ward Jaimie L. , Eickmeyer Sarah M. , Abraham Michael G. , Billinger Sandra A. 
Published: March 2022

Purpose:
Physical activity within the hospital poststroke is recommended for cardiovascular and musculoskeletal health, but no studies have examined cerebrovascular health. We hypothesized that individuals who walked farther distances (FARhigh) during the acute phase of stroke recovery in a hospital setting would have a higher resting middle cerebral artery blood velocity (MCAv) and a greater cerebrovascular response (CVR) to moderate-intensity exercise at 3 months poststroke, compared with individuals who walked shorter distances (FARlow).

Methods:
At 3 months poststroke, we recorded 90 seconds of resting baseline (BL) MCAv, followed by 6 minutes of moderate-intensity exercise. We calculated CVR as the change in MCAv from BL to steady-state exercise. We retrospectively collected the farthest distance walked within the hospital poststroke from the electronic medical record. Participants were classified as FARhigh or FARlow based on the average farthest walking distance.

Results:
Twenty participants completed the study, aged 63 (15) years. Baseline MCAv was not different between groups (P = .07). In comparison with FARlow, we report a higher CVR in FARhigh's ipsilesional (

= 7.38 [5.42] vs

= 2.19 [3.53], P = .02)and contralesional hemispheres (

= 8.15 [6.37] vs

= 2.06 [4.76], P = .04).

Conclusions:
Physical activity during the hospital stay poststroke may support cerebrovascular health after discharge. Prospective studies are needed to support this finding.
RPNI, TMR, and Reset Neurectomy/Relocation Nerve Grafting after Nerve Transection in Headache Surgery
Authors: Gfrerer Lisa , Wong Frankie K. , Hickle Kelli , Eberlin Kyle R. , Valerio Ian L. , Austen William G. 
Published: March 2022

Background:
In the context of headache surgery, greater occipital nerve (GON) transection is performed when the nerve appears severely damaged, if symptoms are recurrent or persistent, and when neuromas are excised. Lesser occipital nerve (LON) excision is commonly performed during the primary decompression surgery. Advanced techniques to address the proximal nerve stump after nerve transection such as regenerative peripheral nerve interface (RPNI), targeted muscle reinnervation (TMR), relocation nerve grafting, and reset neurectomy have been shown to improve chronic pain and neuroma formation. These techniques have not been described in the head and neck region.

Methods:
This article describes RPNI, TMR, and reset neurectomy with GON autograft relocation to prevent chronic pain and neuroma formation after GON/LON transection.

Results:
RPNI and TMR are feasible options in patients undergoing GON/LON transection. Further, relocation nerve grafting with GON autograft relocation is a method that is beneficial in patients with diffuse nerve injury requiring proximal nerve division.

Conclusion:
Advanced nerve reconstruction techniques should be considered in headache surgery following GON/LON transection.
ATYPICAL ENDOGENOUS FUNGAL ENDOPHTHALMITIS CAUSED BY CANDIDA RUGOSA
Authors: Koide Ryohei , Yamamoto Soichiro , Kobayashi Yoshiyuki , Irie Junji , Enaida Hiroshi 
Published: March 2022

Purpose:
The purpose of this study was to report a case of atypical endogenous fungal endophthalmitis caused by Candida rugosa, a rare species of nonalbicans Candida.

Methods:
This report describes a case of a 45-year-old woman who presented with a reduced visual acuity in the right eye in addition to vitreous opacity during breast cancer treatment, which was suspected as fungal endophthalmitis from medical examination and history. Various tests were performed for diagnosis.

Results:
Blood test results were normal, including the blood beta-D-glucan level, and blood cultures were negative. Diagnosis could not be made using systemic computed tomography and magnetic resonance imaging results. Therefore, a lesion sample was collected by using vitrectomy. C. rugosa was identified through DNA (extracted from the lesion sample) analysis using Basic Local Alignment Search Tool. The visual acuity of the right eye improved after vitrectomy.

Conclusion:
We encountered a rare case of atypical endogenous fungal endophthalmitis caused by C. rugosa. Clinicians sometimes encounter invasive candidiasis caused by rare nonalbicans Candida species. DNA analysis using Basic Local Alignment Search Tool is effective for diagnosing such cases.