bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria Are a Potential Therapeutic Target for Alzheimer’s Disease
Authors: Basavalingiah Anish J. , Fang Yan Shi , Yan Shirley ShiDu 
Published: July 2023

Abstract
Mitochondria are organelles that play an essential role in many cellular processes including, but not limited to, oxidative phosphorylation, calcium homeostasis, and apoptosis signaling. Mitochondrial dysfunction is pertinent to the pathology of several neurodegenerative diseases; more specifically, it has been shown to be involved in Alzheimer’s Disease (AD). Moreover, mitochondrial dysfunction in AD manifests through various mechanisms, including opening of mitochondrial permeability transition pore (mPTP), impaired mitochondrial dynamics, dysfunction of mitophagy, and aberrant protein import, among others. No current effectively cure for AD exists and current therapies target the aforementioned mechanisms but struggle to produce positive effects on AD pathology while also being able to cross the blood brain barrier, have high bioavailability, and low levels of cytotoxicity and immunosuppression. Thus, the development of new, clinically viable therapeutic targets and strategies is imperative to furthering the ability to successfully treat AD. This review covers the various levels of mitochondrial dysfunction present in AD pathology, outlines past and current therapeutic targets and strategies, and postulates ways to efficiently discover effective therapies for AD.
Constance Naden
Authors: Stainthorp Clare 
Published: July 2023

Abstract
Constance Naden (1858–1889) was a freethinker whose scientific studies during the 1880s provided a foundation for an idealist-materialist philosophy that rejected dualism. While most scholarship labels her a poet, she identified more strongly as a philosopher. The development of her thought can be traced through her essays and poems, published both independently and in periodicals. Naden initially propounded the theory of Hylo-Idealism, but she became increasingly uneasy with dogmatic advocacy of a single creed and, influenced by Herbert Spencer’s Synthetic Philosophy and the radical freethought movement, came to write more broadly about ethics and the social nature of humanity. Her mature writings focused on Cosmic Identity, a relational system that found unity in diversity and prioritized mutual understanding over individualism. This chapter traces Naden’s development as a thinker, outlining her cumulative philosophical practice through which she synthesized diverse knowledge to develop a secular theory of life and mind.
Pastorals in the City
Authors: Pandit Huzaifa 
Published: July 2023

Abstract
The desire to trace localized nodes of memory and resistance is a recurrent motif in Kashmiri American poet Agha Shahid Ali’s work. A significant part of his oeuvre is dedicated to exploring the subjectivities of postcolonial marginality. This chapter seeks to explore select poems from his critically acclaimed collection The Country without a Post Office. It also explores the collection’s shift from the “restorative nostalgia” that pervades his earlier work to a “reflective nostalgia” of fragmentation, loss, and irreversibility. The poems establish Kashmir as a liminal space of nostalgic longing, reclamation, and loss, where multiple and contradictory trajectories of nation-making converge to articulate counter-discursive allegories of the nation.
The Natural Evolution of Computing
Authors: Duran-Nebreda Salva , Valverde Sergi 
Published: July 2023

Abstract
The evolution of computing is an example of a major, transformative technological adaptation still unfolding in human history. Information technologies are supported by many other knowledge domains that have evolved through a cumulative cultural process, yet at the same time computing affects the tempo and mode of cultural evolution, greatly accelerating innovation processes driven by recombination of present technologies. Additionally, computing has created entire new domains for cumulative cultural evolution, furthering an era dominated by digital economies and media. These new domains offer very desirable qualities for cultural evolution research and digital archaeology, including good coverage in data completeness in widely different aspects of human culture, from social networks to innovation in programming languages. We review the major transitions in information technologies, with especial interest in their connections to a biological evolutionary framework. In particular, software versus hardware evolution poses an interesting example of symbiotic technologies that display strong social dependencies as well as an extrinsic fitness due to energetic and temporal constrains. Properly accounting for the interplay of material and social factors can explain the coexistence of gradualism and punctuated dynamics in cultural and technological evolution.
The Cultural Transmission and Evolution of Folk Narratives
Authors: Tehrani Jamshid J. 
Published: July 2023

Abstract
Folk narratives—such as fairy tales, legends, and fables—are products of tradition, rather than individual authors. As they get passed on from person to person and from generation to generation new variants evolve, some of which catch on and generate new traditions, while others soon fade into extinction. Folklorists have long been interested in documenting and reconstructing these processes, but have often been stymied by the limitations of the folklore record. Cultural Evolution has brought powerful new concepts and methods to investigate the transmission histories of folk narratives, from comparative phylogenetic analyses of the relationships among similar tales from different cultures, to experimental studies of how stories mutate and evolve through oral transmission. This chapter reviews these contributions and considers prospects for future research into the cultural evolution of folk narrative traditions.
Inaugural dropped head syndrome and camptocormia in inflammatory myopathies: a retrospective study
Authors: Robert Marie , Lessard Lola E R , Bouhour Françoise , Petiot Philippe , Fenouil Tanguy , Svahn Juliette , Fiscus Julie , Fabien Nicole , Perard Laurent , Robinson Philip , Durieu Isabelle , Coury Fabienne , Streichenberger Nathalie , Hot Arnaud , Gallay Laure 
Published: July 2023

AbstractObjectivesInaugural axial muscle involvement, defined as dropped head syndrome (DHS) and/or camptocormia (CC), is poorly described in inflammatory myopathies (IM). This study aimed to further characterize IM patients with inaugural DHS/CC, their outcome and care management.MethodsThis retrospective study included IM patients diagnosed between 2000 and 2021. The main inclusion criterion was IM revealed by axial muscle deficit (DHS/CC).ResultsTwenty-seven patients were included; median (IQR) age at first symptoms was 66.0 years (55.5–75.0); 21 were female (77.8%). There were nine IBM, 33.3%, nine overlap myositis (OM, 33.3%), five DM, 18.5%, two immune checkpoint inhibitor-related myositis (7.4%), one focal myositis (3.7%) and one myositis with anti-Hu antibodies (3.7%). Age at first symptoms was ≤70 years in 16 patients (59.3%), including all DM patients and 8/9 OM patients (88.9%). In this group, partial remission of the disease was obtained in 9/16 (56.3%) and complete remission in 1/16 patients (6.3%); regression of DHS/CC was achieved in 3/16 patients (18.8%). Conversely, in the group of 11 patients aged &gt;70 years at first symptoms, there were eight IBM (72.7%). Partial remission was obtained in 5/11 patients (45.5%), the disease was stable in 6/11 patients (54.5%); no complete remission was obtained nor regression of DHS/CC.ConclusionThe analysis of IM patients with inaugural DHS/CC delineates two groups of patients according to the age at first symptoms in terms of clinical and outcome specificities, and proposes an adapted diagnostic and care management approach to prevent long-term complications.
Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis
Authors: Distler Oliver , Ofner Christian , Huscher Dörte , Jordan Suzana , Ulrich Silvia , Stähler Gerd , Grünig Ekkehard , Held Matthias , Ghofrani H Ardeschir , Claussen Martin , Lange Tobias J , Klose Hans , Rosenkranz Stephan , Vonk-Noordegraaf Anton , Vizza C Dario , Delcroix Marion , Opitz Christian , Pausch Christine , Scelsi Laura , Neurohr Claus , Olsson Karen M , Coghlan J Gerry , Halank Michael , Skowasch Dirk , Behr Jürgen , Milger Katrin , Remppis Bjoern Andrew , Skride Andris , Jureviciene Elena , Gumbiene Lina , Miliauskas Skaidrius , Löffler-Ragg Judith , Wilkens Heinrike , Pittrow David , Hoeper Marius M , Ewert Ralf 
Published: July 2023

Abstract

Objectives
Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH.

Methods
We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes.

Results
This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA–PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively).

Conclusions
Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA–PDE5i combination therapy compared with initial monotherapy.
Strained face during sleep in multiple system atrophy: not just a bad dream
Authors: Rosamaria Lecca , Michela Figorilli , Emma Bouniol , Ana Marques , Bruno Pereira , Philippe Derost , Bérangère Debilly , Raffaele Ferri , Monica Puligheddu , Franck Durif , Maria Livia Fantini 
Published: July 2023

Abstract

Study Objectives
Patients with Parkinson’s disease and multiple system atrophy may be subject to sleep state dissociation. Motivated by the fortuitous observation of prominent facial muscle activity during video-polysomnography in patients with multiple system atrophy, we assessed facial motor activity and chin muscle tone during sleep in multiple system atrophy compared to Parkinson’s disease and controls.

Methods
A sleep expert blinded to pathology and sleep stage retrospectively analyzed facial activity in 62 video-polysomnography (11 multiple system atrophy, 38 Parkinson’s disease, and 13 controls). Facial movements were classified into six categories: “Eyes closing/opening,” “Eyebrows frowning,” “Raising eyebrows,” “Smiling,” “Other mouth movements,” and “Strained face,” an expression involving both the superior and inferior parts of the face. Chin electromyography activity was quantified during Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep using the atonia index, a validated algorithm.

Results
Multiple system atrophy patients had an increased number of all facial movements compared to controls during NREM. “Strained face” was significantly more frequent in multiple system atrophy compared to Parkinson’s disease, even after adjusting for the presence of REM sleep behavior disorder (RBD). Atonia index was lower in multiple system atrophy compared to controls and Parkinson’s disease during REM and NREM sleep. This difference remained significant compared to Parkinson’s disease in NREM sleep during N1 and N2 after adjusting for the presence of RBD.

Conclusions
Facial movements during sleep are frequent in multiple system atrophy, “strained face” appears to be a hallmark of this condition. The presence of increased facial activity and elevated muscle tone during all stages of sleep in multiple system atrophy may be a manifestation of sleep state dissociation, reflecting more severe neurodegeneration.
DNMT3B activates FGFR3‐mediated endoplasmic reticulum stress by regulating PTPN2 promoter methylation to promote the development of atherosclerosis
Authors: Zhang Zhiwen , Guo Quan , Zhao Zhenzhou , Nie Ming , Shi Qingbo , Li En , Liu Kaiyuan , Yu Haosen , Rao Lixin , Li Muwei 
Published: July 2023

AbstractEndoplasmic reticulum (ER) stress is closely associated with atherosclerosis (AS). Nevertheless, the regulatory mechanism of ER stress in endothelial cells during AS progression is unclear. Here, the role and regulatory mechanism of DNA (cytosine‐5‐)‐ methyltransferase 3 beta (DNMT3B) in ER stress during AS progression were investigated. ApoE−/− mice were fed with high fat diet to construct AS model in vivo. HE and Masson staining were performed to analyze histopathological changes and collagen deposition. HUVECs stimulated by ox‐LDL were used as AS cellular model. Cell apoptosis was examined using flow cytometry. DCFH‐DA staining was performed to examine ROS level. The levels of pro‐inflammatory cytokines were assessed using ELISA. In addition, MSP was employed to detect PTPN2 promoter methylation level. Our results revealed that DNMT3B and FGFR3 were significantly upregulated in AS patient tissues, whereas PTPN2 was downregulated. PTPN2 overexpression attenuate ox‐LDL‐induced ER stress, inflammation and apoptosis in HUVECs and ameliorated AS symptoms in vivo. PTPN2 could suppress FGFR3 expression in ox‐LDL‐treated HUVECs, and FGFR3 knockdown inhibited ER stress to attenuate ox‐LDL‐induced endothelial cell apoptosis. DNMT3B could negatively regulate PTPN2 expression and positively FGFR2 expression in ox‐LDL‐treated HUVECs; DNMT3B activated FGFR2 expression by increasing PTPN2 promoter methylation level. DNMT3B downregulation repressed ox‐LDL‐induced ER stress, inflammation and cell apoptosis in endothelial cells, which was reversed by PTPN2 silencing. DNMT3B activated FGFR3‐mediated ER stress by increasing PTPN2 promoter methylation level and suppressed its expression, thereby boosting ER stress to facilitate AS progression.
Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis
Authors: Xu Xia , Lu Haiwen , Li Jianxiong , Duan Jielin , Wang Zhongwei , Yang Jiawei , Gu Shuyi , Luo Rongguang , Liang Shuo , Tang Wei , Zhang Fengying , Hang Jingqing , Ge Juan , Lin Xin , Qu Jieming , Jia Xinming , Xu Jinfu 
Published: July 2023

Abstract

Background:
Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 (CARD9) is critical for producing Aspergillus fumigatus-induced (Af-induced) T helper 2 (TH2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9
S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.

Methods:
A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.

Results:
The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus (aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9
S12N, which contributes to its functional alterations to facilitate Af-induced TH2-mediated ABPA development. In terms of mechanism, Card9 wild-type (Card9
WT) expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9
S12N. In addition, ABPA patients with heterozygous CARD9
S12N had increased Af-induced interleukin-5 production.

Conclusion:
Our study provides the genetic evidence showing that the heterozygous mutation of CARD9
S12N, followed by allele expression imbalance of CARD9
S12N, facilitates the development of ABPA.
Spindle Cell Lipoma With Florid Primary Follicular Lymphocytic Hyperplasia: A Novel Association With Potential Diagnostic Pitfalls
Authors: Fattah Yasmin H. , Liu Shuo S. , Susa Joseph , Hanly Andrew , Russo Jacqueline , Karai Laszlo J. 
Published: July 2023

Abstract:
Spindle cell lipoma (SCL) is a benign subcutaneous lipomatous neoplasm with a heterogeneous histologic appearance that varies greatly depending on the amount of fat, collagen, and myxoid stroma, which define the multiple subtypes of SCL, such as fat poor SCL, pseudoangiomatous SCL, and dendritic fibromyxolipoma. Cutaneous lymphoid hyperplasia is a spectrum of benign conditions characterized by reactive B-cell and T-cell cutaneous lymphocytic infiltrates. Cutaneous B-cell lymphoid hyperplasia is a heterogeneous group of non-neoplastic conditions that can be observed as reactive phenomena to infections, medications, allergens, or neoplasms and must be distinguished from cutaneous B-cell lymphomas. Here, we report a novel case of spindle cell lipoma, associated with B-cell primary lymphoid follicular hyperplasia, mixed within the tumor in a peculiar pattern, while discussing potential diagnostic pitfalls with low-grade B-cell lymphomas. This is the first report of such association in the literature.
Serial feature positive and feature negative discrimination learning in a taste avoidance preparation: implications for interoceptive control of behavior
Authors: Huang Shihui , Cerveny Sydney E. , Ruprecht Anna L. , Steere Ethan R. , Davidson Terry L. , Riley Anthony L. 
Published: July 2023

Background
Psychoactive drugs produce interoceptive stimuli that can guide appropriate behaviors by initiating or inhibiting responding.

Objective
The current study investigated whether an interoceptive morphine state produces similar patterns of serial feature positive (FP) and feature negative (FN) discrimination learning under comparable conditions in a taste avoidance design.

Methods
Male Sprague–Dawley rats were trained under 10 cycles of FP or FN discrimination. In the FP task, morphine (10 mg/kg, IP) signaled that a saccharin solution was followed by LiCl (1.2 mEq, IP), while the vehicle (saline) signaled that the LiCl was withheld. In the FN task, the contingency was reversed.

Results
The FP-trained rats acquired the discrimination after three training cycles, consuming significantly less saccharin on morphine, than on vehicle, sessions (P < 0.05). The FN-trained rats acquired the discrimination after six training cycles, consuming more on morphine than on vehicle sessions (P < 0.05). However, FN-trained rats never recovered saccharin consumption to baseline levels and 40% of the rats continued to avoid saccharin (consuming 0 ml) on morphine sessions. Control rats that never received LiCl consumed high levels of saccharin on morphine and vehicle sessions, indicating that morphine did not produce unconditioned suppression of saccharin consumption.

Conclusion
The difficulty to acquire FN discrimination might reflect the limitations of learning about safety contingencies in the taste avoidance design. The rapidity of FP learning when a drug state signals an aversive contingency may have implications for the general role of interoceptive stimuli in the control of behavior.
Sleep-light interventions that shift melatonin rhythms earlier improve perimenopausal and postmenopausal depression: preliminary findings
Authors: Parry Barbara L. , Meliska Charles J. , Sorenson Diane L. , Martinez L. Fernando , Lopez Ana M. , Dawes Sharron E. , Elliott Jeffrey A. , Hauger Richard L. 
Published: July 2023

Abstract

Objective
Testing the hypothesis that a sleep-light intervention, which phase-advances melatonin rhythms, will improve perimenopausal-postmenopausal (P-M; by follicle-stimulating hormone) depression.

Methods
In at-home environments, we compared two contrasting interventions: (1) an active phase-advance intervention: one night of advanced/restricted sleep from 9 pm to 1 am, followed by 8 weeks of morning bright white light for 60 min/d within 30 minutes of awakening, and (2) a control phase-delay intervention: one night of delayed/restricted sleep (sleep from 3 to 7 am) followed by 8 weeks of evening bright white light for 60 min/d within 90 minutes of bedtime. We tested 17 P-M participants, 9 normal controls and 8 depressed participants (DPs) (by Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria). Clinicians assessed mood by structured interviews and subjective mood ratings. Participants wore actigraphs to measure sleep and activity and collected overnight urine samples for the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), before, during, and after interventions.

Results
Baseline depressed mood correlated with delayed 6-SMT offset time (cessation of melatonin metabolite [6-SMT] secretion) (r = +0.733, P = 0.038). After phase-advance intervention versus phase-delay intervention, 6-SMT offset (start of melatonin and 6-SMT decrease) was significantly advanced in DPs (mean ± SD, 2 h 15 min ± 12 min; P = 0.042); advance in 6-SMT acrophase (time of maximum melatonin and 6-SMT secretion) correlated positively with mood improvement (r = +0.978, P = 0.001). Mood improved (+70%, P = 0.007) by both 2 and 8 weeks.

Conclusions
These preliminary findings reveal significantly phase-delayed melatonin rhythms in DP versus normal control P-M women. Phase-advancing melatonin rhythms improves mood in association with melatonin advance. Thus, sleep-light interventions may potentially offer safe, rapid, nonpharmaceutical, well-tolerated, affordable home treatments for P-M depression.