bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities to improve population health: possibilities for healthier food environments
Authors: Lake Amelia A. , Moore Helen J. , Cotton Matthew , O'Malley Claire L.
Published: April 2023

The recent Covid-19 pandemic highlighted stark social inequalities, notably around access to food, nutrition and to green or blue space (i.e. outdoor spaces with vegetation and water). Consequently, obesity is socio-economically patterned by this inequality; and while the environmental drivers of obesity are widely acknowledged, there is currently little upstream intervention. We know that living with obesity contributes to increasing health inequalities, and places healthcare systems under huge strain. Our environment could broadly be described obesogenic, in the sense of supporting unhealthful eating patterns and sedentary behaviour. Evidence points to the existence of nearly 700 UK obesity policies, all of which have had little success. Obesity prevention and treatment has focused on educational and behavioural interventions targeted at individual consumers. A more sustainable approach would be to try and change the environments that promote less healthy eating and high energy intake as well as sedentary behaviour. Approaches which modify the environment have the potential to assist in the prevention of this complex condition. This review paper focuses on the role of wider food environments or foodscapes. While there is an imperfect evidence base relating to the role of the foodscape in terms of the obesity crisis, policy, practice, civic society and industry must work together and take action now, in areas where current evidence suggests change is required. Despite the current cost-of-living crisis, shaping the foodscape to better support healthful eating decisions has the potential to be a key aspect of a successful obesity prevention intervention.
Resilience and vulnerability of discourse-conditioned word order in heritage Spanish
Authors: Hoot Bradley , Leal Tania
Published: April 2023

Heritage speakers—bilinguals who acquire minority languages naturalistically in infancy but are typically majority-language-dominant in adulthood—generally acquire grammars that differ systematically from thebaselineinput received in childhood. Yet not all areas diverge equally; understanding what characterizes divergence or resilience of a given feature is crucial to understanding heritage language acquisition. In this realm, we investigate the discourse-conditioned non-canonical word orders that markinformation focusin Spanish. Focus bears the hallmarks of structures that diverge from the baseline, yet the evidence is mixed. We use an offline forced-choice task and an online self-paced reading task to compare heritage speakers’ judgments and processing to the baseline’s, and we find, echoing recent work, that the heritage speakers largely resemble baseline speakers. We interpret this convergence with reference to seven factors potentially affecting heritage language acquisition and identify one hypothesis—that focus facilitates processing due to its structural and pragmatic salience—as a promising explanation.
Thanatotic Infestation: Ekbom’s Syndrome as an Exordium to Cotard’s Delusion
Authors: Chaudhry Ahmed A. , Hirsch Jack W.
Published: April 2023

Introduction

Ekbom’s delusion as a prelude to Cotard’s syndrome, has not heretofore been described.

Methods

Case study: A 45-year-old woman with a past diagnosis of bipolar disorder with psychotic features was admitted, having been up all night conversing with spirits, proclaiming that she had made a deal with Satan. Convinced that her grandmother was possessed by the devil, she smashed her grandmother’s head with a two-by-four. Results: Mental Status Examination: self conversing with her eyes darting around the room. Poor hygiene. Behavior: guarded and withdrawn. Oriented x2. Speech: hyperverbal. Insight and judgment: poor. Mood: hostile, aggressive, and angry. Thought process disorganized, incongruent, and tangentiality. She was convinced she was infested with little black bugs crawling around her insides which had been placed there by the devil. After two days of olanzapine she reported the bugs were no longer present, but rather that she herself was dead and that her organs were decomposing, which persisted through the remainder of the hospitalization.

Discussion

Neuroimaging abnormalities in Ekbom’s syndrome involve the striatum, basal ganglia (putamen and caudate nucleus), insular and cingulate cortices, cortex (prefrontal, right parietal, and temporal lobes), right lingual and orbitofrontal gyri, and thalamus. In Cotard’s syndrome, abnormalities have been identified in the striatum, frontal and temporal lobes, and right-sided and bilateral hemispheres. An overlap between the delusions exists in the striatum, inferior parietal, and temporal lobes. A single lesion in the nondominant inferior parietal lobe may cause both syndromes, due to its substantial interconnection with the temporo-limbic areas. Since the parietal lobe is also involved in somatosensory processing, peradventure distorted sensory perception with associated sensation of formication may have been the nidus for the delusional infestation as well as a nidus for the perception of thanatos habitus. Such misperception may have then been amplified into a delusion because of a hyperconnection between the parietal lobe and the limbic system. This may represent a variant of the two-factor hypothesis of delusions whereby a distorted sensory perception is then misrepresented in a delusion. Dysfunction of the right hemisphere, which normally acts to censor the left, allows the delusion to manifest. A single lesion of the inferior parietal lobule may be sufficient for both sensory distortions and loss of inhibition of delusional interpretation of distorted sensation by the frontal lobe, yclept the sensorialist hypothesis.

Conclusion

In those with monothematic delusions, the search for transient fluctuation in delusional states may be revealing.

Funding

No Funding
Treatment Success and Psychiatric Stability in Adults With Tardive Dyskinesia: Post Hoc Analyses of Two Long-Term Valbenazine Studies
Authors: Cutler Andrew J. , Jain Rakesh , Bloom Alon , Siegert Scott , Lundt Leslie
Published: April 2023

Introduction

Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with exposure to antipsychotics and other dopamine receptor blocking agents. Effective and comprehensive treatment of TD requires reducing patients’ abnormal involuntary movements without disrupting their psychiatric stability. This can be especially challenging when patients have complex psychiatric conditions (e.g., >1 psychiatric diagnosis) and are taking multiple medications. Valbenazine, a highly potent and selective vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for the once-daily treatment of TD. This post hoc analysis of two long-term studies (KINECT 3, KINECT 4) was conducted to evaluate changes in psychiatric status and clinician- and patient-reported treatment success in study participants who received valbenazine (40 or 80 mg) for 48 weeks.

Methods

Data from KINECT 3 and KINECT 4 were pooled and analyzed in participants categorized by their primary psychiatric diagnosis: schizophrenia/schizoaffective disorder (“SCHZ”) or mood disorder (“MD”). Concomitant medications needed for managing these and other psychiatric or medical conditions were allowed. Treatment success was defined as achieving a rating of “much improved” or “very much improved” at Week 48, as assessed using the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC). Psychiatric stability was monitored using the following scales: Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) in the SCHZ subgroup; Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) in the MD subgroup. Suicidal ideation/behavior was monitored using the Columbia-Suicide Severity Rating Scale.

Results

More than 75% of study participants in the SCHZ subgroup achieved treatment success with valbenazine, based on clinician assessment (CGI-TD, 79.7%) and patient self-report (PGIC, 78.0%). Mean changes from baseline to Week 48 for PANSS scores (positive symptoms [-0.7], negative symptoms [‑0.6], general psychopathology [-1.9], total [-3.2]) and CDSS total score (-0.5) indicated maintenance of psychiatric stability in the SCHZ subgroup. Similar treatment success rates were found in the MD subgroup for both CGI-TD (77.6%) and PGIC (84.5%), with mean changes from baseline in YMRS total score (-1.0) and MADRS total score (+0.3) indicating psychiatric stability was maintained. No emergence of suicidal ideation/behavior was observed during the studies.

Conclusions

Pooled analyses from two 48-week studies indicate that long-term treatment of TD with once-daily valbenazine resulted in substantial clinician- and patient-reported global improvements in TD, while psychiatric stability was maintained regardless of primary psychiatric condition.

Funding

Neurocrine Biosciences, Inc.
Careful, Women! Is Orgasm Worth the Cost of Your Cerebellum? Flibanserin-Induced Cerebellar Dysfunction
Authors: Birwatkar D. , Kalita S. , Hirsch A.R
Published: April 2023

Introduction

Flibanserin, a serotonin antagonist currently indicated for treatment of female sexual dysfunction disorder, has not heretofore been described to worsen cerebellar function. Such a case is presented.

Methods

A 60-year-old woman, 8 months prior to presentation, had an acute onset of fainting and hitting her head into a wall without loss of consciousness. She could not stand up, had left-sided weakness, and vomiting, with garbled, slow speech and severe headache. Findings in the emergency room showed a left cerebellar parenchymal hemorrhage of 3.2 x 3.1 x 2 cm with the epicenter at the dentate nucleus, extending medially towards midline into the cerebellar vermis, with surrounding perilesional edema extending into the middle cerebellar peduncle. Also, 5.2 cm of the hemorrhage extended from the petrous of the tentorium to the cerebellar vermis. Moreover, a ventral left thalamic hemorrhage with subependymal clot at the foramen of Monroe extended into the dependent portion of lateral ventricles without midline shift. Post one month of physical therapy, speech, walking, and coordination improved but she continued to have delayed speech and trouble getting up, with a wide stance.

Results

Neurologic Examination: Cranial Nerve (CN) Examination: CN XI: Sternocleidomastoid hypertrophy, horizontal titubation. Motor examination: Drift test: L pronator drift with L abductor digiti mini sign. Gait examination: heel walking, dystonic posture of L hand. Tandem gait: unstable, wide based. Cerebellar examination: Both (B) finger-to-nose dysmetria, Left > Right. Slow rapid alternating movements (RAM) L Upper Extremity (UE). Due to absent sexual desire she started 100 mg of flibanserin nightly. Maintaining this for 5 weeks, her coordination markedly worsened with poor balance and a need for a cane to ambulate. She would stumble, with a wider gait, and found climbing stairs challenging. Physical examination displayed worse cerebellar function: prominent horizontal titubation. Finger-to-nose—dysmetria L>R. Decreased RAM, L UE. Markedly positive Holmes Rebound phenomenon, Bilateral UE. Tandem gait: unstable. A week post stopping flibanserin, gait and cerebellar examination returned to baseline.

Discussion

The temporal correlation between the use of flibanserin and transient worsening of cerebellar function strongly suggests that this is the causative agent. Since serotonin is essential in cerebellar function, including its action on the cerebellar cortex and deep cerebellar nuclei, it strongly suggests that its action as a serotonin antagonist is the mechanism whereby flibanserin is causing cerebellar symptoms. In those on flibanserin, investigation to detect the presence of cerebellar dysfunction is warranted. Assessment for the presence of cerebellar dysfunction in those who are on anti-serotonin drugs, such as cyproheptadine and methysergide, may be worthwhile.

Funding

No Funding
Vilazodone-Induced Glycolimia
Authors: Jimenez Ayasta Maria de Guadalupe , Hirsch Alan Richard
Published: April 2023

Introduction

Glycolimia is observed in a plethora of medical conditions including burning mouth syndrome, opioid withdrawal, as well as from a variety of medications including vortioxetine, l-methylfolate, lisdexamfetamine, and gabapentin. While vilazodone, an antidepressant with agonist like effects on 5-HT1A receptors, has been found to induce hyperglycemia, it has not heretofore been reported to induce glycolimia. Such a case is described.

Method

Case study: A 60-year-old, left-handed (pathological) male presented with a past history of depression, minimally responsive to a variety of antidepressant medications, was begun on vilazodone, initially 20 mg and gradually increased to 60 mg a day. On 60 mg a day he noticed severe cravings for sweets, which he had never experienced prior to starting vilazodone. He found he had increased consumption, craving sweet foods including cookies and candy. For instance, in a typical day, he would eat eight Oreos, chocolate-covered graham crackers, one pint of ice cream a day, and he would crave sweets even after feeling satiated after consuming a meal. Along with this increased eating, he gained 20 pounds over the 3 months while on the vilazodone. Upon discontinuing the vilazodone, although the weight didn’t change, the sweet cravings resolved.

Results

Abnormalities on: Neurological examination: Mental status examination: Immediate recall: able to remember 6 digits forwards and 3 digits backwards. Motor examination: Drift testing: right inward drift. Gait examination: unstable tandem gait. Neuropsychiatric examination: Go-No-Go test: 6/6 (normal). Animal Fluency Test: 22 (normal).

Discussion

There are myriad mechanisms whereby vilazodone may have induced glycolimia. Possibly due to its antidepressant effects, it increased hedonics, generating appetitive behaviors, including enhanced socialization, sexual, and other consumptive behaviors, including eating. Peradventure it may have enhanced motivation and socialization. Along with socialization, there is escalation in social intercourse, with accompanying commensalism. Along with such consumptive behaviors, we could anticipate glycolimia. As a 5-HT1A receptor agonist, possibly vilazodone may have acted on the arcuate pro-opiomelanocortin neurons associated with hyperphagia, with modulation of energy homeostasis in the serotonin pathway. Alternatively, vilazodone may have triggered an enhanced insulin response with secondary reduction in blood sugar, leading to a homeostatic behavioral response of increased glucose intake. In those who are treated with vilazodone, query as to glycolimia is warranted and warning as to potential manifestations of hyperglycemia should be entertained.

Funding

No Funding
Zuranolone, a Positive Allosteric Modulator of the GABAA Receptor: Hypothesized Mechanism of Action in Major Depressive Disorder
Authors: Stahl Stephen M. , Hammond Rebecca , Garcia Manny , Kyaga Simon , Kotecha Mona , Pollack Mark , Doherty James
Published: April 2023

Major depressive disorder (MDD) is a heterogeneous condition characterized by depressed mood and/or loss of interest/pleasure in activities, among other symptoms. Most currently available treatments for depression were developed on the hypothesis that depressive symptoms arise from a depletion of monoamines within the central nervous system (CNS). However, clinical understanding has advanced to identify brain network dysregulation as the primary driver of depression, with monoamines playing a lesser role. Prolonged inability to regulate brain networks may lead to the core symptoms and clinical presentation of MDD. Depression has been linked to impaired neuronal activity in brain networks (e.g., central executive network [CEN], default mode network [DMN], and salience network [SN]). It is hypothesized that improvement in depressive symptoms may result from restoring balance in brain networks governing mood.

γ-aminobutyric acid (GABA) is critical for maintaining and restoring excitatory-inhibitory balance in the brain and regulating brain networks. Approximately one-third of neurons in the CNS are GABAergic, regulating network activity throughout the brain, including regions involved in mood, sleep, and cognition. GABA activates GABAA receptors (GABAAR), inhibiting neuronal activity through phasic (via synaptic GABAAR) and tonic (via extrasynaptic GABAAR) currents. Tonic GABA currents may play a particularly important role in regulating network activity, since they produce a large net inhibitory effect and are also involved in controlling the excitability of inhibitory interneurons, the key regulators of rhythmic brain network activity.

Zuranolone is an investigational oral GABAAR positive allosteric modulator and neuroactive steroid. In clinical trials, treatment with zuranolone has shown significant improvement over placebo in depressive symptoms in adults with MDD or postpartum depression, with a generally well-tolerated and consistent safety profile.

The hypothesized mechanism of zuranolone differs from monoamine-based antidepressants and from benzodiazepines. Unlike benzodiazepines, which bind to the α/γ subunit interface in synaptic GABAAR and enhance phasic inhibitory currents, zuranolone binds to the α/β subunit interface present in nearly all GABAAR, leading to enhanced phasic (synaptic) and tonic (extrasynaptic) inhibitory currents. Furthermore, in vitro evidence suggests that whereas benzodiazepines are associated with GABAAR downregulation, zuranolone upregulates the surface expression of GABAAR.

In conclusion, by upregulating GABAAR expression and increasing phasic and tonic inhibitory GABAergic signaling, zuranolone may rapidly restore and maintain excitatory-inhibitory balance in brain networks, thus allowing the brain to potentially respond appropriately to internal and external stimuli.

Funding

Sage Therapeutics, Inc., and Biogen Inc.
Inhibitory control in children with agenesis of the corpus callosum compared with typically developing children
Authors: Soon Emilyn , Siffredi Vanessa , Anderson Peter J. , Anderson Vicki A. , McIlroy Alissandra , Leventer Richard J. , Wood Amanda G. , Spencer-Smith Megan M.
Published: April 2023

Objectives:

The developmental absence (agenesis) of the corpus callosum (AgCC) is a congenital brain malformation associated with risk for a range of neuropsychological difficulties. Inhibitory control outcomes, including interference control and response inhibition, in children with AgCC are unclear. This study examined interference control and response inhibition: 1) in children with AgCC compared with typically developing (TD) children, 2) in children with different anatomical features of AgCC (complete vs. partial, isolated vs. complex), and 3) associations with white matter volume and microstructure of the anterior (AC) and posterior commissures (PC) and any remnant corpus callosum (CC).

Methods:

Participants were 27 children with AgCC and 32 TD children 8–16 years who completed inhibitory control assessments and brain MRI to define AgCC anatomical features and measure white matter volume and microstructure.

Results:

The AgCC cohort had poorer performance and higher rates of below average performance on inhibitory control measures than TD children. Children with complex AgCC had poorer response inhibition performance than children with isolated AgCC. While not statistically significant, there were select medium to large effect sizes for better inhibitory control associated with greater volume and microstructure of the AC and PC, and with reduced volume and microstructure of the remnant CC in partial AgCC.

Conclusions:

This study provides evidence of inhibitory control difficulties in children with AgCC. While the sample was small, the study found preliminary evidence that the AC (f2=.18) and PC (f2=.30) may play a compensatory role for inhibitory control outcomes in the absence of the CC.
Ecological validity of cognitive fluctuations in dementia with Lewy bodies
Authors: Webber Troy A. , Lorkiewicz Sara A. , Kiselica Andrew M. , Woods Steven P.
Published: April 2023

Objectives:

Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB.

Methods:

The study sample included 97 participants with consensus-defined DLB from the National Alzheimer’s Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual’s performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual’s performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ).

Results:

Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores).

Conclusions:

Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.
Preferential Trade Agreements, Geopolitics, and the Fragmentation of World Trade
Authors: Dadush Uri , Dominguez Prost Enzo
Published: April 2023

Failure to reestablish an effective World Trade Organization (WTO) dispute settlement procedure, stop the erosion of multilateral rules and end the China–US trade war causes capitals to rethink trade policy. One response is to redouble efforts to strike trade agreements with major trading partners. Already countries accounting for about 78% of world Gross Domestic Product (GDP) are members of mega-regional agreements, and based on our computations, preferential trade agreements (PTAs) will soon cover about two-thirds of world trade. Can PTAs replace a fading WTO or mitigate its effects? Amid deepening geopolitical rifts, how will trade relations among China, the EU, and the US, each a hegemon in their respective regions, evolve, and what will be the impact on smaller economies? In short, how will a trading system based increasingly on PTAs and weak multilateral rules look, and how will nations adapt? Absent reforms, the trading system is likely to fragment progressively into regional blocks organized around the hegemons. Trade within the regional blocks, mainly conducted under a mega-regional agreement, will likely remain quite open and predictable, but without strict multilateral rules and where PTAs are absent (as they are among the hegemons), interregional trade relations will become increasingly uncertain and unstable.
Hong Kong in the age of the PRC’s alienation from the international system: In search of normative consensus
Authors: Wang Chao
Published: April 2023

Hong Kong presents a test case of China’s willingness to adapt Western liberal values of individual freedom and the rule of law in a corner of China. The Western model of governance, along with its common law system and capitalist economic system, has been permitted to operate side by side with the Chinese socialist system within the framework of Chinese sovereignty and the People’s Republic of China’s (PRC) political and legal system. The formation and implementation of the policy of ‘one country, two systems’ (OCTS) entail Chinese law-makers’ selective integration of international and Western rules of governance into the Hong Kong and China context to serve the interests of the PRC party regime. This article explores the approaches taken by the PRC to the governance of Hong Kong in light of the regime’s political and economic goals and how the Western concept of rule of law and autonomy is perceived and substantiated in terms of the communist ideology. The author argues that the intrinsic value of OCTS lies in seeking complementarity and coexistence between the Western liberal norms of governance and Chinese communist ideology, and that this intrinsic value should be upheld and remain in full force to serve as a normative consensus between China and the West.
I Will Give a Little Help to My Friend – Validation of the German Prosocial Behavior Intention Scale (PBIS-G)
Authors: Lorenz Timo , Binder Benjamin
Published: April 2023

Abstract: The present study adapts and investigates the psychometric properties of the German version of the Prosocial Behavioral Intentions Scale (PBIS). The sample included 507 participants. Incongruent with the original study, the PBIS showed low internal consistency (α = .57; ω = .63). The CFA results indicated a good two-dimensional model fit. The PBIS scores showed convergent validity with related instruments. A positive correlation with materialism was observed, so no statements on discriminant validity were made. Additional measurement invariance testing with an existing US sample showed configural measurement invariance, indicating differences in the mode of action in both cultures. Based on these results, the PBIS-G should be used with caution, and further psychometric testing should be conducted to examine discriminant validity and the origin of missing measurement invariance.
Projections of Global Land Runoff Changes and Their Uncertainty Characteristics During the 21st Century
Authors: Miao Chiyuan , Wu Yi , Fan Xuewei , Su Jiajia
Published: April 2023

Quantifying uncertainty in runoff changes has profound implications for future runoff investigations and will support global climate model improvement. We analyze the runoff changes from model outputs of the 5th and 6th Coupled Model Intercomparison Projects (CMIP5 and CMIP6) and decompose the uncertainty of projected runoff changes into three main sources: internal variability, model uncertainty, and scenario uncertainty. The results indicate that 73% and 72% of the global land area, respectively, shows an increase in runoff for CMIP5 and CMIP6 under the high‐emissions scenarios in the long term (2070–2099) relative to 1970–1999, and runoff across all global land increases by 10.8% under the RCP8.5 scenario and 16.1% under SSP5–8.5 during 2070–2099 relative to 1970–1999. Regions with increasing runoff are mainly in Southeast Asia, eastern Africa, the Qinghai‐Tibet Plateau and the high latitudes of the Northern Hemisphere. Model agreement during 2070–2099 for runoff changes under the high‐emissions scenarios is greater than under the low‐emissions scenarios. For uncertainty of relative changes in runoff (RRC) in CMIP6, the contribution from internal variability gradually decreases over time (from 49.2% to 2.0%) while the contribution from scenario uncertainty increases (from 0.6% to 30.0%); this result is similar in CMIP5. Spatially, model uncertainty in RRC has been a major source of uncertainty for CMIP5 and CMIP6, accounting for more than 60% of total uncertainty in most regions. The results of this study help us to better understand the uncertainty in runoff changes and also provide a theoretical basis for developing mitigation measures for future changes.
Astronomical Forcing on Loess Deposition in the Junggar Basin Since the Late Pliocene
Authors: Wang Zhixiang , Zhang Tianfu , Licht Alexis , Cao Mengmeng , Zhang Rui
Published: April 2023

Deciphering dust outbreak frequency in inland Asia during the late Cenozoic is important for predicting future hydroclimate in the arid parts of China. Here, we present an eolian sedimentary sequence in the southern Junggar Basin over the past 3.5 Ma, Northwestern China. Our data provide a minimum age of 3.5 Ma for the Gurbantunggut Desert. Rb/Sr ratios exhibit prominent 405 Kyr eccentricity cycles throughout our record with weak expression 41 Kyr cycles. We interpret this cyclicity as resulting from a strong impact of the global carbon cycle on western China hydroclimate. By contrast, gamma‐ray intensity data displays significant 100‐ and 41‐Kyr cycles after 2.8 Ma, suggesting important variations of the input of westerly derived dust. Our results demonstrate that Westerly derived moisture supply and dust input into inland Asia respond differently to orbital forcing; they suggest that moisture supply and dust transport by the Westerlies are controlled by different drivers since 3.5 Ma.
A Numerical Model for the Interaction of Io‐Generated Alfvén Waves With Jupiter's Magnetosphere and Ionosphere
Authors: Lysak R. L. , Sulaiman A. H. , Bagenal F. , Crary F.
Published: April 2023

The interaction of Io with the corotating magnetosphere of Jupiter is known to produce Alfvén wings that couple the moon to Jupiter's ionosphere. We present first results from a new numerical model to describe the propagation of these Alfvén waves in this system. The model is cast in magnetic dipole coordinates and includes a dense plasma torus that is centered around the centrifugal equator. Results are presented for two density models, showing the dependence of the interaction on the magnetospheric density. Model results are presented for the case when Io is near the centrifugal and magnetic equators as well as when Io is at its northernmost magnetic latitude. The effect of the conductance of Jupiter's ionosphere is considered, showing that a long auroral footprint tail is favored by high Pedersen conductance in the ionosphere. The current patterns in these cases show a U‐shaped footprint due to the generation of field‐aligned current on the Jupiter‐facing and Jupiter‐opposed sides of Io, which may be related to the structure in the auroral footprint seen in the infrared by Juno. A model for the development of parallel electric fields is introduced, indicating that the main auroral footprints of Io can generate parallel potentials of up to 100 kV.
Proposed Origin of the Burns Formation (Meridiani Planum, Mars) by Erosion, Reworking, and Diagenetic Alteration of a Grasberg‐Like Precursor
Authors: McCollom Thomas M. , Hynek Brian M.
Published: April 2023

The sulfate‐rich sandstones of the Burns formation investigated by the Opportunity rover on Meridiani Planum, Mars, are directly underlain by the fine‐grained sedimentary rocks of the Grasberg formation. It was recently shown that, except for differing amounts of MgO and SO3, the Burns and Grasberg rocks have very nearly the same chemical composition, suggesting that both units may be genetically related. Here, quantitative models demonstrate that the chemical composition of the Burns rocks is closely reproduced by the addition of MgO and SO3 to a Grasberg‐like precursor. Comparison with previously proposed chemical models indicates that this new model reproduces the measured Burns rock compositions far better than evaporite models and somewhat better than the addition of sulfur alone to pristine basalt. Based on this result, we propose that the precursor materials for both units were derived from related sources and initially had very similar (or identical) chemical compositions, but magnesium sulfate salts were added to the Burns formation during diagenesis. We further propose an alternative origin of the Burns sandstones that incorporates this new chemical model, which involves (a) deposition of fine‐grained airfall deposits with a composition similar to that of Grasberg, (b) induration and erosion into sand‐sized particles, (c) reworking and deposition of the sand grains by eolian and fluvial processes, and (d) diagenetic alteration of the resulting sediments that includes enrichment in MgO and SO3 through evaporation or freezing of infiltrating groundwater. This new scenario would have substantially different implications for sediment sources, depositional history, and diagenetic processes than other proposed scenarios.
Where Is the Lunar Mantle and Deep Crust at Crisium? A Perspective From the Luna 20 Samples
Authors: Shearer C. K. , Moriarty D. P. , Simon S. B. , Petro N. , Papike J. J.
Published: April 2023

Remote sensing observations have been interpreted to indicate that the Crisium basin‐forming event excavated deep crust and upper mantle. Samples from the highlands adjacent to the Crisium basin returned by Luna 20 (L‐20) bring a unique perspective for evaluating this concept. The magmatic lithologies returned from the noritic Hilly and Furrowed Terrain (nHFT) by L‐20 are coarse‐grained feldspar (>300 μm) with inclusions of pyroxene, and finer‐grained norites, troctolites, spinel troctolites, and gabbros (<100 μm). These two suites represent ferroan anorthosites (FANs) and the Mg‐suite, respectively. There is limited evidence for mantle or deep crustal material within the nHFT samples. Ultramafic rocks such as dunites and orthopyroxenites are absent, and Mg‐rich olivine‐ and orthopyroxene‐bearing‐assemblages are derived from magmatic rocks emplaced in the shallow crust. These lithic fragments represent pre‐Crisium episodes of magmatism (Mg‐suite) and lunar magma ocean products (FANs). The lack of deep lithologies at the L‐20 site seems contradictory to excavation models for Crisium. Mineralogical‐chemical differences suggest a higher FAN component in the rim and that this represents FANs excavated from the deep lunar crust. If it exists, the Mg‐rich olivine previously identified within the Crisium rim is most likely related to deep, complementary versions of the Mg‐suite rocks from L‐20. The material associated with the Crisium basin is not derived from the lunar mantle but represents crustal lithologies from the shallow to deep crust, a substantial mantle component may have been incorporated into the Crisium basin impact melt sheet, or that our “Earth‐analog” for the lunar upper mantle is incorrect.
Estimating Individual Tree Mortality in the Sierra Nevada Using Lidar and Multispectral Reflectance Data
Authors: Hemming‐Schroeder N. M. , Gutierrez A. A. , Allison S. D. , Randerson J. T.
Published: April 2023

Widespread tree mortality events occur during periods of severe drought in temperate conifer forests and are expected to become more frequent in many areas due to climate change. Improved mapping of individual tree mortality is needed to identify risk factors and design effective conservation strategies. In this study, we used National Ecological Observatory Network (NEON) lidar and multispectral reflectance airborne observations to map individual tree mortality over a 160 km2 area during and after the 2012–2016 drought for two sites in California's Sierra National Forest. We used NEON lidar to derive tree locations and crown perimeters and multispectral data to map tree mortality for more than 1 million trees. We found that 25.4% of the trees in our study area died between 2013 and 2017, with considerably higher mortality at the lower‐elevation Soaproot Saddle site. Between 2017 and 2019, an additional 2.0%–2.8% of the trees died each year. Two wildfires in 2020 and 2021 increased tree mortality within burned area perimeters by 49%–89% between 2019 and 2021. Consistent with previous work, we found that tree mortality risk increased as a function of tree height. Tree mortality was positively associated with distance from rivers, trees per hectare, and decreasing slope at the lower elevation site. In contrast, increasing slope was positively associated with tree mortality at the higher elevation site. Our approach and dataset provide a means to study the combined effects of drought and wildfire on tree mortality and may improve projections of forest resilience under a changing climate.
A Window Into Eastern Mediterranean Productivity Conditions Over Three Pliocene Precession‐Forced Climate Cycles
Authors: Cutmore A. , Bale N. , De Lange G. J. , Nijenhuis I. A. , Lourens L. J.
Published: April 2023

Here, we explore the importance of export productivity versus anoxia in the formation of sedimentary layers with enhanced total organic carbon (TOC) content. We use geochemical, sedimentological and micropaleontological records from two SW Sicily outcropping successions, Lido Rossello (LR) and Punta di Maiata (PM), over three Early Pliocene precession‐forced climate cycles (4.7–4.6 million years ago [Ma]). Gray marls, deposited during precession minima, show enhanced TOC in both records. We suggest that basin‐wide, low‐oxygenated bottom‐waters, resulting from freshwater‐induced stratification during precession minimum, was integral to preserving gray marl TOC. Furthermore, prolonged eastern Mediterranean stratification may have produced a deep chlorophyll maximum (DCM), leading to “shade‐flora” dominated productivity. The LR succession displays two unique laminated layers containing enhanced TOC. These laminations do not occur at specific times in the precession cycle or in time‐equivalent PM samples. They are likely to have been produced by an intermittent dysoxic/anoxic pool at LR, caused by a local depression, which enhanced TOC preservation. Consequently, the laminations provide a rare window into “true” eastern Mediterranean productivity conditions during precession maxima, as organic matter is typically poorly preserved during these period due to enhanced ventilation. The laminated “windows” indicate that eastern Mediterranean export productivity may not have been significantly lower during precession maxima compared to precession minima, as previously thought. During these periods, productivity conditions are likely to have been comparable to the modern eastern Mediterranean, with a spring‐bloom caused by enhanced winter/spring deep‐water mixing preceding a summer “shade‐flora” bloom caused by a summer‐stratification induced DCM.
Influence of Bed Roughness on Flow and Turbulence Structure Around a Partially‐Buried, Isolated Freshwater Mussel
Authors: Lazzarin T. , Constantinescu G. , Di Micco L. , Wu H. , Lavignani F. , Lo Brutto M. , Termini D. , Viero D. P.
Published: April 2023

The present study uses eddy‐resolving numerical simulations to investigate how bed roughness affects flow and turbulence structure around an isolated, partially‐buried mussel (Unio elongatulus) aligned with the incoming flow. The rough‐bed simulations resolve the flow past the exposed part of a gravel bed, whose surface is obtained from a laboratory experiment that also provides some additional data for validation of the numerical model. Results are also discussed for the limiting case of a horizontal smooth bed. Additionally, the effects of varying the level of burial of the mussel inside the substrate and the discharge through the two mussel siphons are investigated via a set of simulations in which the ratio between the median diameter of the (gravel) particles forming the rough bed, d50, and the height of the exposed part of the mussel, h, varies between 0.10 and 0.22. The increase of the bed roughness is associated with a strong amplification of the turbulence kinetic energy in the near‐wake region. Increasing the bed roughness and/or reducing h intensifies the interactions of the eddies generated by the bed particles with the base and tip vortices induced by the active filtering and by the mussel shell, respectively, which, in turn, induces a more rapid dissipation of these vortices. Increasing the bed roughness also reduces the strength of the main downwelling flow region forming in the wake. The strong downwelling near the symmetry plane is the main reason why the symmetric wake shedding mode dominates in the smooth bed simulations with negligible active filtering. By contrast, the anti‐symmetric wake shedding mode dominates in the simulations conduced with a high value of the bed roughness. The mean streamwise drag force coefficient for the emerged part of the shell and the dilution of the excurrent siphon jet increase with increasing bed roughness.
Hot Rocks: Interpreting Extremes of Earth Surface Temperatures From the Geologic Record
Authors: Suarez Marina B.
Published: April 2023

How hot can we expect Greenhouse Earth to have been in the past and the future? This is a question that deep‐time paleoclimatologists have long investigated. In a new paper by Fetrow et al. (2022), https://doi.org/10.1029/2022PA004517, deconvolving the depositional environments and burial history of continental carbonates deposited during known greenhouse climates, such as the Cretaceous, highlight the way Earth scientists can embark on understanding the clumped isotope derived temperatures and properly interpreting such temperatures.
Emotion-induced brain activation across the menstrual cycle in individuals with premenstrual dysphoric disorder and associations to serum levels of progesterone-derived neurosteroids
Authors: Stiernman Louise , Dubol Manon , Comasco Erika , Sundström-Poromaa Inger , Boraxbekk Carl-Johan , Johansson Maja , Bixo Marie
Published: April 2023

Premenstrual dysphoric disorder (PMDD) is a debilitating disorder characterized by severe mood symptoms in the luteal phase of the menstrual cycle. PMDD symptoms are hypothesized to be linked to an altered sensitivity to normal luteal phase levels of allopregnanolone (ALLO), a GABAA-modulating progesterone metabolite. Moreover, the endogenous 3β-epimer of ALLO, isoallopregnanolone (ISO), has been shown to alleviate PMDD symptoms through its selective and dose-dependent antagonism of the ALLO effect. There is preliminary evidence showing altered recruitment of brain regions during emotion processing in PMDD, but whether this is associated to serum levels of ALLO, ISO or their relative concentration is unknown. In the present study, subjects with PMDD and asymptomatic controls underwent functional magnetic resonance imaging (fMRI) in the mid-follicular and the late-luteal phase of the menstrual cycle. Brain responses to emotional stimuli were investigated and related to serum levels of ovarian steroids, the neurosteroids ALLO, ISO, and their ratio ISO/ALLO. Participants with PMDD exhibited greater activity in brain regions which are part of emotion-processing networks during the late-luteal phase of the menstrual cycle. Furthermore, activity in key regions of emotion processing networks - the parahippocampal gyrus and amygdala - was differentially associated to the ratio of ISO/ALLO levels in PMDD subjects and controls. Specifically, a positive relationship between ISO/ALLO levels and brain activity was found in PMDD subjects, while the opposite was observed in controls. In conclusion, individuals with PMDD show altered emotion-induced brain responses in the late-luteal phase of the menstrual cycle which may be related to an abnormal response to physiological levels of GABAA-active neurosteroids.
Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain
Authors: Lu Ke , Wang Qingyun , Jiang Hua , Li Jun , Yao Zhou , Huang Yongcan , Chen Jianquan , Zhang Yejia , Xiao Guozhi , Hu Xueyu , Luo Zhuojing , Yang Liu , Tong Liping , Chen Di
Published: April 2023

Spine degeneration is an aging-related disease, but its molecular mechanisms remain unknown, although elevated β-catenin signaling has been reported to be involved in intervertebral disc degeneration. Here, we determined the role of β-catenin signaling in spinal degeneration and in the homeostasis of the functional spinal unit (FSU), which includes the intervertebral disc, vertebra and facet joint and is the smallest physiological motion unit of the spine. We showed that pain sensitivity in patients with spinal degeneration is highly correlated with β-catenin protein levels. We then generated a mouse model of spinal degeneration by transgenic expression of constitutively active β-catenin in Col2+ cells. We found that β-catenin-TCF7 activated the transcription of CCL2, a known critical factor in osteoarthritic pain. Using a lumbar spine instability model, we showed that a β-catenin inhibitor relieved low back pain. Our study indicates that β-catenin plays a critical role in maintaining spine tissue homeostasis, its abnormal upregulation leads to severe spinal degeneration, and its targeting could be an avenue to treat this condition.
CYP1B1 inhibits ferroptosis and induces anti-PD-1 resistance by degrading ACSL4 in colorectal cancer
Authors: Chen Congcong , Yang Yabing , Guo Yanguan , He Jiashuai , Chen Zuyang , Qiu Shenghui , Zhang Yiran , Ding Hui , Pan Jinghua , Pan Yunlong
Published: April 2023

Immune checkpoint blockade (ICB) is a promising treatment strategy for colorectal cancer (CRC) patients. However, most CRC patients do not response well to ICB therapy. Increasing evidence indicates that ferroptosis plays a critical role in immunotherapy. ICB efficacy may be enhanced by inducing tumor ferroptosis. Cytochrome P450 1B1 (CYP1B1) is a metabolic enzyme that participates in arachidonic acid metabolism. However, the role of CYP1B1 in ferroptosis remains unclear. In this study, we demonstrated that CYP1B1 derived 20-HETE activated the protein kinase C pathway to increase FBXO10 expression, which in turn promoted the ubiquitination and degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4), ultimately inducing tumor cells resistance to ferroptosis. Furthermore, inhibiting CYP1B1 sensitized tumor cells to anti-PD-1 antibody in a mouce model. In addition, CYP1B1 expression was negatively correlated with ACSL4 expression, and high expression indicates poor prognosis in CRC. Taken together, our work identified CYP1B1 as a potential biomarker for enhancing anti-PD-1 therapy in CRC.
Sestrin2-mediated disassembly of stress granules dampens aerobic glycolysis to overcome glucose starvation
Authors: Li Mingyue , Thorne Rick Francis , Wang Ruijie , Cao Leixi , Cheng Fangyuan , Sun Xuedan , Wu Mian , Ma Jianli , Liu Lianxin
Published: April 2023

Sestrins are a small gene family of pleiotropic factors whose actions promote cell adaptation to a range of stress conditions. In this report we disclose the selective role of Sestrin2 (SESN2) in dampening aerobic glycolysis to adapt to limiting glucose conditions. Removal of glucose from hepatocellular carcinoma (HCC) cells inhibits glycolysis associated with the downregulation of the rate-limiting glycolytic enzyme hexokinase 2 (HK2). Moreover, the accompanying upregulation of SESN2 through an NRF2/ATF4-dependent mechanism plays a direct role in HK2 regulation by destabilizing HK2 mRNA. We show SESN2 competes with insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) for binding with the 3′-UTR region of HK2 mRNA. Interactions between IGF2BP3 and HK2 mRNA result in their coalescence into stress granules via liquid-liquid phase separation (LLPS), a process which serves to stabilize HK2 mRNA. Conversely, the enhanced expression and cytoplasmic localization of SESN2 under glucose deprivation conditions favors the downregulation of HK2 levels via decreases in the half-life of HK2 mRNA. The resulting dampening of glucose uptake and glycolytic flux inhibits cell proliferation and protect cells from glucose starvation-induced apoptotic cell death. Collectively, our findings reveal an intrinsic survival mechanism allowing cancer cells to overcome chronic glucose shortages, also providing new mechanistic insights into SESN2 as an RNA-binding protein with a role in reprogramming of cancer cell metabolism.