bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orexin contributes to eupnea within a critical period of postnatal development
Authors: Spinieli Richard L. , Ben Musa Ruwaida , Kielhofner Jane , Cornelius-Green Jennifer , Cummings Kevin J. 
Published: August 2021

Orexin neurons are active in wakefulness and mostly silent in sleep. In adult rats and humans, orexin facilitates the hypercapnic ventilatory response but has little effect on resting ventilation. The influence of orexin on breathing in the early postnatal period, and across states of vigilance, have not been investigated. This is relevant as the orexin system may be impaired in Sudden Infant Death Syndrome (SIDS) cases. We addressed three hypotheses: 1) orexin provides a drive to breathe in infancy; 2) the effect of orexin depends on stage of postnatal development; and 3) orexin has a greater influence on breathing in wakefulness compared with sleep. Whole body plethysmography was used to monitor breathing of infant rats at three ages: postnatal days ( P) 7–8, 12–14, and 17–19. Respiratory variables were analyzed in wakefulness (W), quiet sleep (QS), and active sleep (AS), following suvorexant (5 mg/kg ip), a dual orexin receptor antagonist, or vehicle (DMSO). Effects of suvorexant on ventilatory responses to graded hypercapnia ([Formula: see text] = 0.02, 0.04, 0.06), hypoxia ([Formula: see text] = 0.10), and hyperoxia ([Formula: see text] = 1.0) at P12–14 were also tested. At P12–14, but not at other ages, suvorexant significantly reduced respiratory frequency in all states, reduced the ventilatory equivalent in QW and QS, and increased [Formula: see text] to ∼5 mmHg. Suvorexant had no effect on ventilatory responses to graded hypercapnia or hypoxia. Hyperoxia eliminated the effects of suvorexant on respiratory frequency at P12–14. Our data suggest that orexin preserves eupneic frequency and ventilation in rats, specifically at ∼2 wk of age, perhaps by facilitating tonic peripheral chemoreflex activity.
PDSS1-Mediated Activation of CAMK2A-STAT3 Signaling Promotes Metastasis in Triple-Negative Breast Cancer
Authors: Yu Tian-Jian , Liu Ying-Ying , Li Xiao-Guang , Lian Bi , Lu Xun-Xi , Jin Xi , Shao Zhi-Ming , Hu Xin , Di Gen-Hong , Jiang Yi-Zhou 
Published: August 2021

Abstract

Genomic alterations are crucial for the development and progression of human cancers. Copy-number gains found in genes encoding metabolic enzymes may induce triple-negative breast cancer (TNBC) adaptation. However, little is known about how metabolic enzymes regulate TNBC metastasis. Using our previously constructed multiomic profiling of a TNBC cohort, we identified decaprenyl diphosphate synthase subunit 1 (PDSS1) as an essential gene for TNBC metastasis. PDSS1 expression was significantly upregulated in TNBC tissues compared with adjacent normal tissues and was positively associated with poor survival among patients with TNBC. PDSS1 knockdown inhibited TNBC cell migration, invasion, and distant metastasis. Mechanistically, PDSS1, but not a catalytically inactive mutant, positively regulated the cellular level of coenzyme Q10 (CoQ10) and intracellular calcium levels, thereby inducing CAMK2A phosphorylation, which is essential for STAT3 phosphorylation in the cytoplasm. Phosphorylated STAT3 entered the nucleus, promoting oncogenic STAT3 signaling and TNBC metastasis. STAT3 phosphorylation inhibitors (e.g., Stattic) effectively blocked PDSS1-induced cell migration and invasion in vitro and tumor metastasis in vivo. Taken together, our study highlights the importance of targeting the previously uncharacterized PDSS1/CAMK2A/STAT3 oncogenic signaling axis, expanding the repertoire of precision medicine in TNBC.

Significance:
A novel metabolic gene PDSS1 is highly expressed in triple-negative breast cancer tissues and contributes to metastasis, serving as a potential therapeutic target for combating metastatic disease.
Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer
Authors: Hashimoto Ayumi , Sarker Debashis , Reebye Vikash , Jarvis Sheba , Sodergren Mikael H. , Kossenkov Andrew , Sanseviero Emilio , Raulf Nina , Vasara Jenni , Andrikakou Pinelopi , Meyer Tim , Huang Kai-Wen , Plummer Ruth , Chee Cheng E. , Spalding Duncan , Pai Madhava , Khan Shahid , Pinato David J. , Sharma Rohini , Basu Bristi , Palmer Daniel , Ma Yuk-Ting , Evans Jeff , Habib Robert , Martirosyan Anna , Elasri Naouel , Reynaud Adeline , Rossi John J. , Cobbold Mark , Habib Nagy A. , Gabrilovich Dmitry I. 
Published: August 2021

Abstract

Purpose:
To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models.

Experimental Design:
We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38).

Results:
MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC–targeted immunotherapy.

Conclusions:
This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).
Relevance of pRB Loss in Human Malignancies
Authors: Mandigo Amy C. , Tomlins Scott A. , Kelly William K. , Knudsen Karen E. 
Published: August 2021

Abstract
The retinoblastoma tumor suppressor protein (pRB) is a known regulator of cell-cycle control; however, recent studies identified critical functions for pRB in regulating cancer-associated gene networks that influence the DNA damage response, apoptosis, and cell metabolism. Understanding the impact of these pRB functions on cancer development and progression in the clinical setting will be essential, given the prevalence of pRB loss of function across disease types. Moreover, the current state of evidence supports the concept that pRB loss results in pleiotropic effects distinct from tumor proliferation. Here, the implications of pRB loss (and resultant pathway deregulation) on disease progression and therapeutic response will be reviewed, based on clinical observation. Developing a better understanding of the pRB-regulated pathways that underpin the aggressive features of pRB-deficient tumors will be essential for further developing pRB as a biomarker of disease progression and for stratifying pRB-deficient tumors into more effective treatment regimens.
Circulating and Intratumoral Adrenal Androgens Correlate with Response to Abiraterone in Men with Castration-Resistant Prostate Cancer
Authors: Mostaghel Elahe A. , Marck Brett T. , Kolokythas Orpheus , Chew Felix , Yu Evan Y. , Schweizer Michael T. , Cheng Heather H. , Kantoff Phillip W. , Balk Steven P. , Taplin Mary-Ellen , Sharifi Nima , Matsumoto Alvin M. , Nelson Peter S. , Montgomery R. Bruce 
Published: August 2021

Abstract

Purpose:
In metastatic castration-resistant prostate cancer (mCRPC) low serum androgens prior to starting abiraterone acetate (AA) is associated with more rapid progression. We evaluated the effect of AA on androgens in castration-resistant prostate cancer (CRPC) metastases and associations of intratumoral androgens with response.

Experimental Design:
We performed a phase II study of AA plus prednisone in mCRPC. The primary outcome was tissue testosterone at 4 weeks. Exploratory outcomes were association of steroid levels and genomic alterations with response, and escalating AA to 2,000 mg at progression.

Results:
Twenty-nine of 30 men were evaluable. Testosterone in metastatic biopsies became undetectable at 4 weeks (P &lt; 0.001). Serum and tissue dehydroepiandrosterone sulfate (DHEAS) remained detectable in many patients and was not increased at progression. Serum and tissue DHEAS in the lowest quartile (pretreatment), serum DHEAS in the lowest quartile (4 weeks), and undetectable tissue DHEAS (on-therapy) associated with rapid progression (20 vs. 48 weeks, P = 0.0018; 20 vs. 52 weeks, P = 0.0003; 14 vs. 40 weeks, P = 0.0001; 20 vs. 56 weeks, P = 0.02, respectively). One of 16 men escalating to 2,000 mg had a 30% PSA decline; 13 developed radiographic progression by 12 weeks. Among patients with high serum DHEAS at baseline, wild-type (WT) PTEN status associated with longer response (61 vs. 33 weeks, P = 0.02).

Conclusions:
Low-circulating adrenal androgen levels are strongly associated with an androgen-poor tumor microenvironment and with poor response to AA. Patients with CRPC with higher serum DHEAS levels may benefit from dual androgen receptor (AR)-pathway inhibition, while those in the lowest quartile may require combinations with non–AR-directed therapy.
Hippocampal–Cortical Encoding Activity Predicts the Precision of Episodic Memory
Authors: Korkki Saana M. , Richter Franziska R. , Simons Jon S. 
Published: August 2021

Abstract
Our recollections of past experiences can vary in both the number of specific event details accessible from memory and the precision with which such details are reconstructed. Prior neuroimaging evidence suggests the success and precision of episodic recollection to rely on distinct neural substrates during memory retrieval. In contrast, the specific encoding mechanisms supporting later memory precision, and whether they differ from those underlying successful memory formation in general, are currently unknown. Here, we combined continuous measures of memory retrieval with model-based analyses of behavioral and neuroimaging data to tease apart the encoding correlates of successful memory formation and mnemonic precision. In the MRI scanner, participants encoded object-scene displays and later reconstructed features of studied objects using a continuous scale. We observed overlapping encoding activity in inferior prefrontal and posterior perceptual regions to predict both which object features were later remembered versus forgotten and the precision with which they were reconstructed from memory. In contrast, hippocampal encoding activity significantly predicted the precision, but not overall success, of subsequent memory retrieval. The current results align with theoretical accounts proposing the hippocampus to be critical for representation of high-fidelity associative information and suggest a contribution of shared cortical encoding mechanisms to the formation of both accessible and precise memory representations.
Overlapping Neuronal Population Responses in the Human Parietal Cortex during Visuospatial Attention and Arithmetic Processing
Authors: Liu Nan , Pinheiro-Chagas Pedro , Sava-Segal Clara , Kastner Sabine , Chen Qi , Parvizi Josef 
Published: August 2021

Abstract
Engagement of posterior parietal cortex (PPC) in visuospatial attention and arithmetic processing has been extensively documented using neuroimaging methods. Numerous studies have suggested a close connection between visuospatial attention and arithmetic processing. However, the extant evidence in humans stems from neuroimaging methods that have relied on group analyses without much knowledge about the profile of neurophysiological engagement within localized neuronal populations at the individual brain level. Hence, it has remained unclear if the overlap of two functions in the PPC is the product of averaging, or they truly stem from a common profile of activity within the same neuronal populations in the human PPC. In the current study, we leveraged the anatomical precision and high signal-to-noise ratio of intracranial electrocorticography and probed the engagement of discrete PPC neuronal populations in seven neurosurgical patients (n = 179 total PPC sites covered; 26 sites on average per individual participant). We aimed to study the extent of parietal activations within each individual brain during visuospatial attention versus arithmetic tasks and the profile of electrophysiological responses within a given recording site during these tasks. Our findings indicated that about 40% of PPC sites did not respond to either visuospatial attention or arithmetic stimuli—or episodic memory conditions that were used as an adjunct control condition. Of those that were activated during either visuospatial attention or arithmetic conditions, a large majority showed overlapping responses during both visuospatial attention and arithmetic conditions. Most interestingly, responses during arithmetic processing were greatest in sites along the intraparietal sulcus region showing preference to contralateral, instead of ipsilateral, visual probes in the visuospatial attention task. Our results provide novel data about the relationship between numerical and spatial orientation at the neuronal population level and shed light on the complex functional organization of the PPC that could not be attained with noninvasive methods.
Longitudinal Clinical and Patient-Reported Outcomes After Transversus Abdominis Release for Complex Hernia Repair With a Review of the Literature
Authors: Christopher Adrienne N. , Morris Martin P. , Barrette Louis-Xavier , Patel Viren , Broach Robyn B. , Fischer John P. 
Published: August 2021

Purpose Posterior component separation with transversus abdominis release (TAR) enables medial myofascial flap advancement in complex abdominal wall reconstruction. Here, we add to a growing body of literature on TAR by assessing longitudinal clinical and patient-reported outcomes (PROs) after complex ventral hernia repair (VHR) with TAR. Methods Adult patients undergoing VHR with TAR between 10/15/2015 and 1/15/2020 were retrospectively identified. Patients with parastomal hernias and <12 months of follow-up were excluded. Clinical outcomes and PROs were assessed. Results Fifty-six patients were included with a median age and body mass index of 60 and 30.8 kg/m2, respectively. The average hernia defect was 384 cm2 [IQR 205-471], and all patients had retromuscular mesh placed. The most common complications were delayed healing (19.6%) and seroma (14.3%). There were no cases of mesh infection or explantation. Previous hernia repair and concurrent panniculectomy were risk factors for developing complications ( P < .05). One patient (1.8%) recurred at a median follow-up of 25.2 months [IQR 18.2-42.4]. Significant improvement in disease-specific PROs was maintained throughout the follow-up period (before to after P < .05). Conclusion Transversus abdominis release is a safe and efficacious technique to achieve fascial closure and retromuscular mesh in the repair of complex hernia defects.
Decreased Facial Emotion Recognition in Elderly Patients With Hearing Loss Reflects Diminished Social Cognition
Authors: Saatci Özlem , Geden Hakan , Güneş Çiftçi Halide , Çiftçi Zafer , Arıcı Düz Özge , Yulug Burak 
Published: August 2021

Objective: The main objective of this research was to evaluate the correlation between the severity of hearing loss and the facial emotional recognition as a critical part of social cognition in elderly patients. Methods: The prospective study was comprised of 85 individuals. The participants were divided into 3 groups. The first group consisted of 30 subjects older than 65 years with a bilateral pure-tone average mean >30 dB HL. The second group consisted of 30 subjects older than 65 years with a PTA mean ≤30 dB HL. The third group consisted of 25 healthy subjects with ages ranging between 18 and 45 years and a PTA mean ≤25 dB HL. A Facial Emotion Identification Test and a Facial Emotion Discrimination Test were administered to all groups. Results: Elderly subjects with hearing loss performed significantly worse than the other 2 groups on the facial emotion identification and discrimination tests ( P < .05). Appealingly, they identified a positive emotion, “happiness,” more accurately in comparison to the other negative emotions. Conclusions: Our results suggest that increased age might be associated with decreased facial emotion identification and discrimination scores, which could be deteriorated in the presence of significant hearing loss.
Transformations of the Cambridge Critique
Authors: Schefold Bertram 
Published: August 2021

The debate on capital theory has recently been revived. Reswitching had led to agnosticism regarding the substitution of capital for labour in consequence of changes in the rate or profit. The paradoxes of reswitching and reverse capital deepening now turn out to be rare for theoretical reasons, and this is confirmed empirically, but new results also show that the possibilities of substitution between capital and labour are quite limited; their ratio is given within narrow limits by technology, if the choice of techniques is efficient. This is a new critique of neoclassical theory; it confirms the complementary theories of distribution advanced by the Cambridge economists: the share of profits is influenced by effective demand (Kaldor) and by the level of interest rates as an element of cost (Sraffa). Both theories presuppose the stability of the capital-output ratio. This finding also sheds light on the options of central banks regarding the fixation of interest rates. JEL Code: B51, C67, D57, E11, E13, E44
Using Public Health Surveillance Data to Determine Hepatitis C Virus Exposure Among Live-Born Infants in Tennessee, 2013-2017
Authors: Wingate Heather , Sizemore Lindsey , Black Jennifer , Heth Zachary , Talley Pamela , Patrick Stephen W. , Wester Carolyn 
Published: August 2021

Objective Maternal hepatitis C virus (HCV) infection reported on birth certificates has been shown to underestimate HCV infection. We sought to determine the usefulness of HCV surveillance data for (1) quantifying the number of HCV-positive reproductive-aged women with a live birth, (2) comparing maternal HCV surveillance data with reported HCV infection status on birth certificates, and (3) delineating past versus current maternal infection to identify true perinatal exposures. Methods We extracted data from January 1, 2013, through December 31, 2017, on birth certificate indication of HCV exposure from the Tennessee Birth Statistical File, and we ascertained indication of HCV exposure by using laboratory data from the Tennessee National Electronic Disease Surveillance System (NEDSS) Base System (NBS). We conducted a sensitivity analysis comparing birth certificate indication of HCV exposure with HCV laboratory data to determine whether true perinatal exposure had occurred. Results During the study period, 6731 mothers with live births in Tennessee reported having HCV infection during pregnancy: 3295 (49.0%) had both laboratory and birth certificate indication of HCV infection, 2130 (31.6%) had indication of HCV infection on the laboratory report only, and 1306 (19.4%) had indication of HCV infection on the birth certificate only. Conclusions Using data from a public health HCV surveillance system with birth certificate data may improve the identification of HCV-infected pregnant women and perinatally exposed infants. Surveillance systems that include complete reporting of all HCV RNA results can be used to distinguish past from present maternal HCV infection to focus limited public health resources on currently infected mothers and their exposed infants.
Smiles behind the masks: A systematic review and narrative synthesis exploring how family members of seriously ill or dying patients are supported during infectious disease outbreaks
Authors: Bloomer Melissa J , Walshe Catherine 
Published: August 2021

Background: Infection control measures during infectious disease outbreaks can have significant impacts on seriously ill and dying patients, their family, the patient-family connection, coping, grief and bereavement. Aim: To explore how family members of patients who are seriously ill or who die during infectious disease outbreaks are supported and cared for during serious illness, before and after patient death and the factors that influence family presence around the time of death. Design: Systematic review and narrative synthesis. Data sources: CINAHL, Medline, APA PsycInfo and Embase were searched from inception to June 2020. Forward and backward searching of included papers were also undertaken. Records were independently assessed against inclusion criteria. Included papers were assessed for quality, but none were excluded. Findings: Key findings from 14 papers include the importance of communication and information sharing, as well as new ways of using virtual communication. Restrictive visiting practices were understood, but the impact of these restrictions on family experience cannot be underestimated, causing distress and suffering. Consistent advice and information were critical, such as explaining personal protective equipment, which family found constraining and staff experienced as affecting interpersonal communication. Cultural expectations of family caregiving were challenged during infectious disease outbreaks. Conclusion: Learning from previous infectious disease outbreaks about how family are supported can be translated to the current COVID-19 pandemic and future infectious disease outbreaks. Consistent, culturally sensitive and tailored plans should be clearly communicated to family members, including when any restrictions may be amended or additional supports provided when someone is dying.