bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dolutegravir Plus Lamivudine Dual-Drug Regimen in Treatment-Naive HIV-1—Infected Patients With High-Level Viral Load: Preliminary Data From the Real World
Authors: Zhao Fang , Rao Man , Chen Weimei , Cai Kanru , Zhang Lukun , Xu Liumei , Sun Liqing , Liu Xiaoning , He Yun , Wang Hui 
Published: September 2022

Background:
Some inpatients with HIV-RNA ≥500,000 copies/mL in China need to use 2-drug regimen for some reasons, although limited data are available for dolutegravir plus lamivudine (3TC) in those patients with ultra-high viral loads.

Methods:
We conducted a single-center retrospective–prospective study in China and enrolled 42 ART-naive HIV-infected inpatients who use a once-daily 2-drug regimen because of various reasons (drug interaction, renal impairment, age, and other related comorbidities).They were divided into 2 groups, low viral load group (baseline viral load <500,000 copies/mL, n = 20) and high viral load group (baseline viral load ≥500,000 copies/mL, n = 22). All patients were followed up for 48 weeks.

Results:
The median of baseline viral load was 5.74 log10 copies/mL and CD4+ T-cell count was 59 cells/μL. At week 48, there was no significant difference (P = 0.598) in proportions of participants with HIV-1 RNA <50 copies/mL [90%, 95% confidence interval (CI) (75.6% to 104.4%) in low viral load groups vs 95.5%, 95% CI (86.0% to 104.9%) in high viral load groups]. No differences were found in mean increase of CD4+ T-cell count from baseline between 2 groups (218 ± 122 vs 265 ± 127 cells/μL, P = 0.245). There is no grade 3 or higher treatment-related adverse events and none discontinued treatment because of adverse events.

Conclusions:
The results of our study in real world support dolutegravir + 3TC dual regimen as a promising therapy option for treatment-naive HIV-infected patient with baseline viral load ≥500,000 copies/mL.
Lesion-Specific Metabolic Alterations in Relapsing-Remitting Multiple Sclerosis Via 7 T Magnetic Resonance Spectroscopic Imaging
Authors: Lipka Alexandra , Niess Eva , Dal-Bianco Assunta , Hangel Gilbert J. , Rommer Paulus S. , Strasser Bernhard , Motyka Stanislav , Hingerl Lukas , Berger Thomas , Hnilicová Petra , Kantorová Ema , Leutmezer Fritz , Kurča Egon , Gruber Stephan , Trattnig Siegfried , Bogner Wolfgang 
Published: September 2022

Background
Magnetic resonance spectroscopic imaging (MRSI) of the brain enables in vivo assessment of metabolic alterations in multiple sclerosis (MS). This provides complementary insights into lesion pathology that cannot be obtained via T1- and T2-weighted conventional magnetic resonance imaging (cMRI).

Purpose
The aims of this study were to assess focal metabolic alterations inside and at the periphery of lesions that are visible or invisible on cMRI, and to correlate their metabolic changes with T1 hypointensity and the distance of lesions to cortical gray matter (GM).

Methods
A 7 T MRSI was performed on 51 patients with relapsing-remitting MS (30 female/21 male; mean age, 35.4 ± 9.9 years). Mean metabolic ratios were calculated for segmented regions of interest (ROIs) of normal-appearing white matter, white matter lesions, and focal regions of increased mIns/tNAA invisible on cMRI. A subgroup analysis was performed after subdividing based on T1 relaxation and distance to cortical GM. Metabolite ratios were correlated with T1 and compared between different layers around cMRI-visible lesions.

Results
Focal regions of, on average, 2.8-fold higher mIns/tNAA than surrounding normal-appearing white matter and with an appearance similar to that of MS lesions were found, which were not visible on cMRI (ie, ~4% of metabolic hotspots). T1 relaxation was positively correlated with mIns/tNAA (P ≤ 0.01), and negatively with tNAA/tCr (P ≤ 0.01) and tCho/tCr (P ≤ 0.01). mIns/tCr was increased outside lesions, whereas tNAA/tCr distributions resembled macroscopic tissue damage inside the lesions. mIns/tCr was −21% lower for lesions closer to cortical GM (P ≤ 0.05).

Conclusions
7 T MRSI allows in vivo visualization of focal MS pathology not visible on cMRI and the assessment of metabolite levels in the lesion center, in the active lesion periphery and in cortical lesions. This demonstrated the potential of MRSI to image mIns as an early biomarker in lesion development.
Intense Diffuse Lung Uptake Due to Interstitial Pneumopathy Related to Polyangiitis Granulomata in 68Ga-PSMA-11 PET/CT
Authors: Moreau Aurélie , Pretet Valentin , Paquet Emilie , Giraudet Anne Laure , Kryza David 
Published: September 2022

Abstract
We reported the case of a 73-year-old man for whom a prostatic adenocarcinoma with synchronous bone metastases was diagnosed. Because his disease was progressing despite several lines of chemotherapy and hormonotherapy, he was screened with a 68Ga-PSMA PET/CT for a possible 177Lu-PSMA-617 therapy. The examination demonstrated an intense diffuse bone uptake related to the known bone involvement. It also showed an unexpected diffuse and intense lung uptake, secondary to an active polyangiitis granulomata. This intense lung uptake prohibits the radioligand therapy.
Hair-Bearing Expanded Scalp Flap for Total Beard Reconstruction in Patients With Chin and Submental Postburn Scars
Authors: Ding Jianke , Chu Feifei , Yu Zhou , Liu Chaohua , Yang Qing , Tang Yinke , Ma Xianjie 
Published: September 2022

Background:
Loss of beard in adult male caused by severe burn may cause cosmetic and psychological problems for these patients. Reconstruction of the beard with hair-bearing skin flaps in similar color and texture of the surrounding tissues remains a challenge.

Methods:
Eight male patients suffered from submental postburn scar and beard loss were treated by using the hair-bearing expanded scalp flap. A 1000 mL nephroid tissue expander was first implanted under the frontal and mid scalp. After a 3 to 4-month tissue expansion, the expanded hair-bearing scalp flap based on bilateral superficial temporal vessels were raised and transferred for beard reconstruction, and the cutaneous pedicles were curled into tubes. Delay and division of the pedicles were performed 3 to 4 weeks after flap transfer.

Results:
Eight male patients with postburn scar and beard loss were successfully treated with no major complication. One patient suffered from edge necrosis at distal end of the flap and healed after daily dressing change. Chin and submental areas were repaired by expanded scalp flap and total beard was reconstructed at the same time. All donor sites were closed directly without skin grafting.

Conclusions:
The modified expanded bipedicled scalp flap provides an easy and reliable way for total beard reconstruction and large-scale submental scars repairment.
Ocrelizumab for Post-Alemtuzumab Paradoxical Disease Activity in Highly Active Multiple Sclerosis
Authors: Adamec Ivan , Habek Mario 
Published: September 2022

Abstract
Alemtuzumab is a humanized anti-CD52 antibody that is registered for treatment of highly active relapsing-remitting multiple sclerosis. Disease activity after alemtuzumab treatment is infrequent. It may be a result of lack of lymphocyte depletion due to development of neutralizing autoantibodies. On the other hand, severe disease activity has been described after alemtuzumab, which is suggested to be caused by B-cell hyperpopulation. We present a case of a person with multiple sclerosis with severe disease activation after alemtuzumab administration that may represent paradoxical B cell–mediated disease activity. The patient was successfully treated with ocrelizumab.
Cultural Considerations in Fahr's Syndrome: A Case Report
Authors: Ots Heather D. , Zagade Tarek A. , Chung James P. , Torres Giovanni , Petri Justin D. 
Published: September 2022

Objectives
Many psychiatrists, and other providers alike, find difficulty integrating a culture-centered approach to clinical practice and navigating the challenges when they arise. We call attention to the ongoing challenges of addressing the cultural barriers between patient and physician.

Methods
We present a case of an African patient with a rare case of Fahr's syndrome whose clinical diagnostic course was complicated by culture and language barriers.

Results
The patient's hospital course was challenged by cultural and language barriers that were difficult to integrate into her care, likely contributing to a prolonged diagnostic course and hospitalization.

Conclusions
Cultural considerations in medicine can enhance patient-physician relationships and ultimately strengthen clinical outcomes.
CD4-binding site immunogens elicit heterologous anti-HIV-1 neutralizing antibodies in transgenic and wildtype animals
Authors: Gristick Harry B. , Hartweger Harald , Loewe Maximilian , van Schooten Jelle , Ramos Victor , Oliviera Thiago Y. , Nishimura Yoshiaki , Koranda Nicholas S. , Wall Abigail , Yao Kai-Hui , Poston Daniel , Gazumyan Anna , Wiatr Marie , Horning Marcel , Keeffe Jennifer R. , Hoffmann Magnus A.G. , Yang Zhi , Abernathy Morgan E. , Dam Kim-Marie A. , Gao Han , Gnanapragasam Priyanthi N.P. , Kakutani Leesa M. , Pavlovitch-Bedzyk Ana Jimena , Seaman Michael S. , Howarth Mark , McGuire Andrew T. , Stamatatos Leonidas , Martin Malcolm A. , West Anthony P. , Nussenzweig Michel C. , Bjorkman Pamela J. 
Published: September 2022

SummaryPassive transfer of broadly neutralizing anti-HIV-1 antibodies (bNAbs) protects against infection, and therefore eliciting bNAbs by vaccination is a major goal of HIV-1 vaccine efforts. bNAbs that target the CD4-binding site (CD4bs) on HIV-1 Env are among the most broadly active, but to date, responses elicited against this epitope in vaccinated animals have lacked potency and breadth. We hypothesized that CD4bs bNAbs resembling the antibody IOMA might be easier to elicit than other CD4bs antibodies that exhibit higher somatic mutation rates, a difficult-to-achieve mechanism to accommodate Env’s N276gp120 N-glycan, and rare 5-residue light chain complementarity determining region 3s (CDRL3s). As an initial test of this idea, we developed IOMA germline-targeting Env immunogens and evaluated a sequential immunization regimen in transgenic mice expressing germline-reverted IOMA. These mice developed CD4bs epitope-specific responses with heterologous neutralization, and cloned antibodies overcame neutralization roadblocks including accommodating the N276gp120 glycan, with some neutralizing selected HIV-1 strains more potently than IOMA. The immunization regimen also elicited CD4bs-specific responses in animals containing polyclonal antibody repertoires. Thus, germline-targeting of IOMA-class antibody precursors represents a potential vaccine strategy to induce CD4bs bNAbs.
Locus-specific proteomics identifies new aspects of the chromatin context involved in V region somatic hypermutation
Authors: Yu GuoJun , Duan Zhi , Zhang Yongwei , Aguilan Jennifer T , Sidoli Simone , Scharff Matthew D 
Published: September 2022

AbstractActivation-induced cytidine deaminase (AID) somatically hypermutates the immunoglobulin heavy chain variable region (IGHV) gene to create the antibody diversity required to resist infections. This hypermutational process involves many pathways including transcription, DNA structural change and repair. While many of the proteins involved have been identified, their relative abundance, organization and regulation have not been resolved and additional factors and pathways need to be identified. To identify the proteome occupying IGHV, we have utilized dCas9-APEX targeted by guide RNAs to biotinylate and enrich the proteins associated with the mutating V region chromatin in the Ramos human B cell line and compared them to the non-mutating downstream constant region (C) chromatin. We identified hundreds of proteins specifically enriched on the V or C region. We confirmed the functionality of selected factors by examining the changes in the V region-specific proteome after inhibiting transcriptional elongation and somatic mutation with the Dot1L inhibitor EPZ004777.SummaryLocus-specific proteomics using dCas9-APEX identifies new aspects of the chromatin context involved in V region somatic hypermutation (SHM) in the human Ramos B cell line. An inhibitor of Dot1L which participates in SHM is used to identify functional SHM-related factors.
Improving biome labeling for tens of thousands of inaccurately annotated microbial community samples based on neural network and transfer learning
Authors: Wang Nan , Wang Teng , Ning Kang 
Published: September 2022

AbstractMicrobiome samples are accumulating at a fast speed, leading to millions of accessible microbiome samples in the public databases. However, due to the lack of strict meta-data standard for data submission and other reasons, there is currently a non-neglectable proportion of microbiome samples in the public database that have no annotations about where these samples were collected, how they were processed and sequenced, etc., among which the missing information about collection niches (biome) is one of the most prominent. The lack of sample biome information has created a bottleneck for mining of the microbiome data, making it difficult in applications such as sample source tracking and biomarker discovery. Here we have designed Meta-Sorter, a neural network and transfer learning enabled AI method for improving the biome labeling of thousands of microbial community samples without detailed biome information. Results have shown that out of 16,507 samples that have no detailed biome annotations, 96.65% could be correctly classified, largely solving the missing biome labeling problem. Interestingly, we succeeded in classify 250 samples, which were sampled from benthic and water column but vaguely labeled as “Marine” in MGnify, in more details and with high fidelity. What’s more, many of successfully predicted sample labels were from studies that involved human-environment interactions, for which we could also clearly differentiated samples from environment or human. Taken together, we have improved the completeness of biome label information for thousands of microbial community samples, facilitating sample classification and knowledge discovery from millions of microbiome samples.
NAD(H) homeostasis is essential for host protection mediated by glycolytic myeloid cells in tuberculosis
Authors: Pacl Hayden T. , Chinta Krishna C. , Reddy Vineel P. , Nadeem Sajid , Sevalkar Ritesh R. , Nargan Kierveshan , Lumamba Kapongo , Naidoo Threnesan , Glasgow Joel N. , Agarwal Anupam , Steyn Adrie J. C. 
Published: September 2022

AbstractMycobacterium tuberculosis (Mtb) disrupts glycolytic flux in infected myeloid cells through an unclear mechanism. Flux through the glycolytic pathway in myeloid cells is inextricably linked to the availability of NAD+, which is maintained by NAD+ salvage and lactate metabolism. Using lung tissue from tuberculosis (TB) patients and myeloid deficient LDHA (LdhaLysM−/−) mice, we demonstrate that glycolysis in myeloid cells is essential for protective immunity in TB. Glycolytic myeloid cells are essential for the early recruitment of multiple classes of immune cells and the protective effects of IFNγ. We identified NAD+ depletion as central to the glycolytic inhibition caused by Mtb. Lastly, we show that the NAD+ precursor nicotinamide exerts a host-directed, antimycobacterial effect, and that nicotinamide prophylaxis and treatment reduces Mtb lung burden in vivo. These findings provide new insight into how Mtb alters host metabolism through perturbation of NAD(H) homeostasis and reprogramming of glycolysis, highlighting this pathway as a potential therapeutic target.
An ensemble of interconverting conformations of the elemental paused transcription complex creates regulatory options
Authors: Kang Jin Young , Mishanina Tatiana V. , Bao Yu , Chen James , Llewellyn Eliza , Liu James , Darst Seth A. , Landick Robert 
Published: September 2022

SUMMARYTranscriptional pausing underpins regulation of cellular RNA synthesis but its mechanism remains incompletely understood. Sequence-specific interactions of DNA and RNA with the dynamic, multidomain RNA polymerase (RNAP) trigger reversible conformational changes at pause sites that temporarily interrupt the nucleotide addition cycle. These interactions initially rearrange the elongation complex (EC) into an elemental paused EC (ePEC). ePECs can form longer-lived PECs by further rearrangements or interactions of diffusible regulators. For both bacterial and mammalian RNAPs, a half-translocated state in which the next DNA template base fails to load into the active site appears central to the ePEC. Some RNAPs also swivel interconnected modules that may stabilize the ePEC. However, it is unclear if swiveling and half-translocation are requisite features of a single ePEC state or if multiple ePEC states exist. Here we use cryo-EM analysis of ePECs with different RNA–DNA sequences combined with biochemical probes of ePEC structure to define an interconverting ensemble of ePEC states. ePECs occupy either pre- or half-translocated states but do not always swivel, indicating that difficulty in forming the post-translocated state at certain RNA–DNA sequences may be the essence of the ePEC. The existence of multiple ePEC conformations has broad implications for transcriptional regulation.SIGNIFICANCETranscriptional pausing provides a hub for gene regulation. Pausing provides a timing mechanism to coordinate regulatory interactions, co-transcriptional RNA folding and protein synthesis, and stop signals for transcriptional termination. Cellular RNA polymerases (RNAPs) are complex, with multiple mobile modules shifting positions to control its catalytic activity and pause RNAP in response to DNA-encoded pause signals. Understanding how these modules move to enable pausing is crucial for a mechanistic understanding of gene regulation. Our results clarify the picture significantly by defining multiple states among which paused RNAP partitions in response to different pause signals. This work contributes to an emerging theme wherein multiple interconverting states of the RNAP proceed through a pathway (e.g., initiation or pausing), providing multiple opportunities for regulation.
An iterative learning control with learnable band extension for the nanopositioning stage
Authors: Huang Chengsi , Yang Zhichao , Li Jiedong 
Published: September 2022

Purpose
Due to the advantages of fast response, high positioning precision and large stiffness, the piezoelectric-actuated nanopositioning stage is widely used in the micro/nanomachining fields. However, due to the inherent nonlinear hysteresis of the piezoelectric-actuator, the positioning accuracy of nanopositioning stage is greatly degraded. Besides, the nanopositioning stage is always performed with repetitive trajectories as the reference signals in applications, which makes the hysteresis behavior periodic. To this end, an adaptive resonance suppression iterative learning control (ARS-ILC) is proposed to address the hysteresis effect. With this effort, the positioning accuracy of the nanopositioning stage is improved.

Design/methodology/approach
The hysteresis behavior is identified by the Prandtl–Ishlinskii model. By establishing a convergence function, it is demonstrated that the learnable band of ILC is restricted by the lightly damping resonance of nanopositioning stage. Then, an adaptive notch filter (ANF) with constrained poles and zeros is adopted to suppress the resonant peak. Finally, online stability supervision (OSS) is used to ensure that the estimated frequency converges to the resonant frequency.

Findings
A series of experiments were carried out in the nanopositioning stage, and the results validated that the OSS is available to ensure the convergence of the ANF. Furthermore, the learnable band was extended via ARS-ILC; thus, the hysteresis behavior of nanopositioning stage has been canceled.

Originality/value
Due to high accuracy and easy implementation, the ARS-ILC can be used in not only nanopositioning stage control but other fabrication process control with repetitive motion.
Analyzing external environmental, strategic alliance, and strategic alliance of Kingdom of Saudi Arabia firms – an empirical research
Authors: Abdalkrim Gafar , Guizani Moncef 
Published: September 2022

PurposeThis study investigates the effect of strategic internal critical factors on strategic alliance performance in an emerging market, the Kingdom of Saudi Arabia.Design/methodology/approachMultivariate statistical analysis technique Partial Least Square-Squared Equation Model is used for data analysis considering a survey of 260 alliance managers.FindingsEnvironmental complexity moderates the relationship between strategic internal critical factors and strategic performance. A significant positive effect of strategic internal critical factors on corporation strategic performance was found. It suggests that environment and strategic alliance enable alliance managers and decision-makers to translate alliance strategies and improve the overall organization’s performance outcome, productivity, efficiency, availability of a product and profitability.Practical implicationsThe findings disseminate beneficial implications for alliance managers regarding how they can best use their capability to maximize alliance performance. Realizing the antecedents of strategic alliance performance allows a manager to be sensitive about the influent factors and try to improve the alliance performance.Originality/valueThis paper shows how to create associations between interfirm coordination as a framework of new ventures for implementing radical technological change, firm performance in the post-innovation period, industry and firm innovative output.
Luxury is dead, long live luxury! Resonance as an alternative lens to advance our understanding of an eternal desire and a global business
Authors: Duma Fabio 
Published: September 2022

PurposeIn contemporary business and marketing literature luxury is mainly approached from the perspectives of production, communication and consumption. The author argues that to understand the phenomenon in the future, different, more contextualized and human-focused lenses and methodologies are needed. He ventures out into philosophy, sociology and anthropology to broaden the perspective on the matter and proposes resonance, the theory of successful world relations, as an alternative view on luxury and luxury consumption.Design/methodology/approachThe paper is based on the authors' reflections and an extensive review of literature, including contributions from different academic disciplines.FindingsWith introduction of resonance the author provides an alternative theoretical and practical lens on a multifaceted and dynamic phenomenon that nurtures lucrative markets which must adapt and fundamentally redefine themselves in response to changing social, ecological, technological and economic circumstances and evolving customer needs pointing towards a new social paradigm.Originality/valueThe author presents a critical view on luxury and enriches the discussion in the marketing and business-related literature with the perspectives of philosophy, sociology and other disciplines, linking the phenomenon to resonance theory and the notions of rebellion and escape. The paper suggests new ways of intellectually, scientifically and commercially engaging with the notion luxury and aims at serving as a springboard for further research.