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Objective This study examined patterns of breast cancer screening during the COVID-19 pandemic. Methods This retrospective study was approved by the Georgetown University IRB. Review of electronic medical records identified screening mammograms and breast MRIs between March 13, 2018 and December 31, 2020, for female patients aged 18 to 85 years. Descriptive statistics characterized patterns of breast cancer screening before and during the COVID-19 pandemic. Logistic regression analyses examined whether receipt of breast MRI differed over time and demographic and clinical factors associated with receipt of breast MRI in 2020. Results Data included 47 956 mammography visits in 32 778 patients and 407 screening breast MRI visits in 340 patients. After an initial decrease following the declaration of the COVID-19 pandemic, both screening mammograms and screening breast MRI demonstrated early recovery. Although the mammography receipt remained sustained, the receipt of screening breast MRI decreased in late 2020. Odds of having a breast MRI did not differ between 2018 and 2019 (OR = 1.07; 95% CI = 0.92%–1.25%; P = 0.384) but were significantly lower in 2020 versus 2019 (OR = 0.76; 95% CI = 0.61%–0.94%; P = 0.011). No demographic or clinical factors were associated with receipt of breast MRI during the COVID-19 pandemic (all P-values ≥0.225). Conclusion Breast cancer screening decreased following the declaration of the COVID-19 pandemic. Although both procedures demonstrated early recovery, the rebound in screening breast MRI was not sustained. Interventions promoting return to screening breast MRI may be needed for high-risk women.

Up-converted self-trapped exciton luminescence via seven-phonon absorption in the Na/Bi-alloyed Cs2AgInCl6 lead-free double perovskite is reported.

Background: Diabetic cardiomyopathy (DCM) is the leading cause of diabetic death as the final occurrence of heart failure and arrhythmia. Traditional Chinese medicine is usually used to treat various diseases including diabetes. Objective: This study sought to investigate the effects of Traditional Chinese medicine supplementing Qi and activating blood circulation (SAC) in DCM. Methods: After the construction of the DCM model by streptozotocin (STZ) injection and high glucose/fat diet feeding, rats were administered intragastrically with SAC. Then, cardiac systolic/diastolic function was evaluated by detecting left ventricular systolic pressure (LVSP), maximal rate of left ventricular pressure rise (+LVdp/dtmax), and fall (-LVdp/dtmax), heart rate (HR), left ventricular ejection fraction (EF), LV fractional shortening (FS) and left ventricular end-diastolic pressure (LVEDP). Masson’s and TUNEL staining were used to assess fibrosis and cardiomyocyte apoptosis. Results: DCM rats exhibited impaired cardiac systolic/diastolic function manifested by decreasing LVSP, +LVdp/dtmax, -LVdp/dtmax, HR, EF and FS, and increasing LVEDP. Intriguingly, traditional Chinese medicine SAC alleviated the above-mentioned symptoms, indicating a potential role in improving cardiac function. Masson’s staining substantiated that SAC antagonized the increased collagen deposition and interstitial fibrosis area and the elevations in protein expression of fibrosis-related collagen I and fibronectin in heart tissues of DCM rats. Furthermore, TUNEL staining confirmed that traditional Chinese medicine SAC also attenuated cardiomyocyte apoptosis in DCM rats. Mechanically, DCM rats showed the aberrant activation of the TGF-β/Smad signaling, which was inhibited after SAC. Conclusion: SAC may exert cardiac protective efficacy in DCM rats via the TGF-β/Smad signaling, indicating a new promising therapeutic approach for DCM.

Purpose To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel). Methods Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score). Results Fifty-one patients were randomized to crofelemer (n = 26) or control (n = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea. Conclusion Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID. Trial registration Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.

Objective. Ruanmailing oral solution consists of 16 herbs, has anti-lipid peroxidation activity, protects vascular endothelial cells, and improves vascular elasticity. It is an effective drug for the treatment of atherosclerosis (AS). The objective of this study was to investigate the mechanism underlying the antiatherosclerotic effects of Ruanmailing oral solution. Methods. Macrophages were isolated, cultured, and divided into the macrophage control; macrophage foam cell; and low-, medium-, and high-concentration Ruanmailing groups. Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay, and the expression levels of inward-rectifier potassium ion channel 2.1 (Kir2.1) and tumor necrosis factor (TNF)-α were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. Results. CCK-8 assay results showed that the tested concentrations of Ruanmailing solution did not affect macrophage proliferation. RT-PCR and Western blot assays indicated that TNF-α expression increased significantly with the formation of macrophage foam cells (P

Background: CID occurs in up to 80% of patients with breast cancer who receive trastuzumab (H), pertuzumab (P), and a taxane, with grade 3 experienced by 8-12% of patients. Crofelemer is an extract of the Croton lechleri tree that inhibits luminal chloride efflux, implicated in the HP-related CID. We hypothesized crofelemer would prevent diarrhea in patients with HER2+ breast cancer receiving HP and docetaxel or paclitaxel, with/without carboplatin (THP or TCHP) in the neoadjuvant, adjuvant, or metastatic setting. Clinical trial information: NCT02910219. Methods: Adult patients with HER2+ any stage breast cancer, scheduled to receive at least 3 consecutive cycles of TCHP (docetaxel, carboplatin, trastuzumab and pertuzumab) or THP (trastuzumab and pertuzumab with paclitaxel or docetaxel), normal organ function, PS 0-2, who provided written informed consent were randomized 1:1 to receive crofelemer 125 mg PO 2x/day during cycles 1 and 2 of chemotherapy or no scheduled prophylactic medication. Randomization was stratified according to chemotherapy regimen. The primary endpoint was the incidence of CID of any grade for ≥2 consecutive days assessed by NCI CTCAE v4.0. Provider reported outcomes were collected during clinic visits and prospectively documented in clinical notes. Patient reported outcomes (PRO) were collected from patient diaries. Secondary endpoints were incidence of all grades and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; frequency of break through anti-diarrheal medications use; and FACIT-D total score. Fisher’s exact test was used for comparing binary and categorical variables and summary statistics and Wilcoxon test for ordinal grade variables. The trial was designed to detect a 40% absolute decrease in incidence of CID (from 60% to 20%), two-sided significance level of 0.10. Results: A total of 53 patients were enrolled between 02/21/2017- 08/25/2020 on crofelemer (n=27) or control (n=26) arms. One patient withdrew consent prior to starting protocol procedures and was substituted. Early treatment discontinuation occurred in 7 cases: complications of diarrhea (n=1, control group), chemotherapy regimen changed for other cause than diarrhea (n=4) and non-compliance with trial procedures (n=2). 29 patients had early stage disease treated with TCHP; 23 patients had metastatic disease treated with THP (16 with paclitaxel and 7 with docetaxel). The primary endpoint was not statistically different between the two groups. The incidence of Grade 2 or greater diarrhea was 20.9% vs 26.4% of patients receiving crofelemer or placebo respectively in cycle 1, and 9.5% vs 41.1% in cycle 2 (Table). Results were consistent between provider assessments and patient reported outcomes (PRO). Detailed description of pooled cycle 1-2 data using correlated ordinal model and the additional secondary endpoints will be presented. Conclusions: Although there was no significant difference between crofelemer and control for diarrhea for 2 or more consecutive days in both cycles, there was a clinically meaningful difference between the crofelemer and control groups in maximum within-cycle diarrhea ordinal CTCAE grade diarrhea. These data are supportive for further testing of crofelemer in the ongoing randomized Phase 3 trial OnTARGET (NCT04538625). CycleCTCAE bCrofelemerControlPDiarrhea >= 2 consecutive days a168.069.6NS d265.272.2Maximum diarrhea grade a1Grade 0 c33.321.1NS eGrade 145.852.6Grade 216.721.1Grade 34.25.3Grade 40.00.02Grade 0 c38.117.60.0261 eGrade 152.441.2Grade 29.523.5Grade 30.017.6Grade 40.00.0Maximum diarrhea grade PRO f1Grade 0 c4.08.7NS eGrade 172.039.1Grade 216.043.5Grade 38.08.7Grade 40.00.02Grade 0 c9.10.00.0361 eGrade 181.866.7Grade 24.522.2Grade 34.511.1Grade 40.00.0aProvider assessedbCTCAE: NCI Common Terminology Criteria for Adverse Events v4.0cGrade 0: no diarrheadFisher''s exact testeWilcoxon rank sum testfPRO: Patient reported outcomes Citation Format: Paula R Pohlmann, Deena Graham, Tianmin Wu, Yvonne Ottaviano, Mahsa Mohebtash, Shweta Kurian, Donna McNamara, Filipa Lynce, Robert Warren, Asma Dilawari, Suman Rao, Candace Mainor, Nicole Swanson, Ming Tan, Claudine Isaacs, Sandra M. Swain. Halt-d: A randomized open label phase 2 study of crofelemer for the prevention of chemotherapy induced diarrhea (cid) in patients with breast cancer receiving trastuzumab, pertuzumab, and a taxane [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-09.

Background Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, are approved to treat hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) and are associated with hematologic toxicity. African American women, who are underrepresented in CDK4/6 inhibitor clinical trials, may experience worse neutropenia because of benign ethnic neutropenia. The authors specifically investigated the hematologic safety of palbociclib in African American women with HR-positive/HER2-negative ABC. Methods PALINA was a single-arm, open-label, investigator-initiated study of palbociclib (125 mg daily; 21 days on and 7 days off) plus endocrine therapy (ET) in African American women who had HR-positive/HER2-negative ABC and a baseline absolute neutrophil count ≥1000/mm3 (ClinicalTrials.gov identifier NCT02692755). The primary outcome was the proportion of patients who completed 12 months of therapy without experiencing febrile neutropenia or treatment discontinuation because of neutropenia. Single nucleotide polymorphism analysis was used to assess Duffy polymorphism status. Results Thirty-five patients received ≥1 dose of palbociclib plus ET; 19 had a Duffy null polymorphism (cytosine/cytosine). There were no reports of febrile neutropenia or permanent study discontinuation because of neutropenia. Significantly more patients with the Duffy null versus the wild-type variant had grade 3 and 4 neutropenia (72.2% vs 23.1%; P = .029) and required a palbociclib dose reduction (55.6% vs 7.7%; P = .008). Patients with the Duffy null versus the wild-type variant had lower overall relative dose intensity (mean ± SD, 81.89% ± 15.87 and 95.67% ± 5.89, respectively; P = .0026) and a lower clinical benefit rate (66.7% and 84.6%, respectively). Conclusions These findings suggest that palbociclib is well tolerated in African American women with HR-positive/HER2-negative ABC. Duffy null status may affect the incidence of grade 3 neutropenia, dose intensity, and possibly clinical benefit.

As promising new-generation sunlight-harvesting materials, hybrid organic-inorganic perovskites (HOIPs) have attracted a great deal of attention because of their outstanding advantage of high-power conversion efficiency and low-cost experimental synthesis. Tremendous chemical space and complexity of HOIPs, however, seriously hinder the applications of traditional trial-and-error and high-throughput density functional theory (HT-DFT) methods. Although the machine learning methods successfully accelerate the discovery of new stable and nontoxic HOIPs for photovoltaics, the performance of the current machine learning strategy is still severely limited by the quality of training input database, resulting in a large chemical space for further exploration. A progressive machine learning strategy is therefore introduced in the current study to investigate the impact of an input database enriched by a previous machine learning study, aiming to provide a more reliable and accurate approach to deep mining of the hidden HOIPs for sunlight harvesting. Enhancement in the performance indicators of a progressive machine learning strategy indicates that the data set generated by the previous round of machine learning study could dramatically enrich the training input database and improve its quality. Further DFT validations confirm that 96 out of 209 machine learning selected candidates have promising band gaps for light harvesting, so the prediction success rate of the current work is significantly enhanced compared to that of the previous work. Current study thence successfully verifies the feasibility of a progressive machine learning strategy for accurate and deep mining of hidden novel functional materials.

Background: There are significant racial disparities in breast cancer outcomes between African American women (AAW) and Caucasian women (CW) in the US. It has been reported that AAW have more chemotherapy dose reductions than CW which results in worse clinical outcomes (Schneider BP et al. JCO Precis Oncol 2017). Given the high incidence of benign ethnic neutropenia (BEN) in AAW, we sought to evaluate the hematological safety of palbociclib in this group of patients. A polymorphism (SNP rs2814778 at chromosome 1q23.2) in the Duffy Antigen Receptor Chemokine (DARC) gene is implicated in the pathophysiology of BEN. AAW have been historically underrepresented in clinical trials including studies that led to the FDA approval of palbociclib. This diversity gap can compromise the generalizability of clinical trial results and further exacerbate minority health disparities. Methods: PALINA is a phase II study that evaluated the hematological safety of palbociclib with endocrine therapy (ET) in 35 AAW with HR positive HER2 negative advanced breast cancer (ABC) and ANC ≥1,000 cells/mm3. Eligible patients were self-identified as African, African-American or Black, PS 0-2 and had not received a prior CDK4/6 inhibitor (CDK4/6i). Treatment included palbociclib 125mg daily for 21 days followed by 7 days off and either an aromatase inhibitor (AI) or fulvestrant per investigator discretion. Maximum time allowed on study was 12 months. Responding patients could continue palbociclib off trial. Presence of the Duffy null polymorphism as a predictive marker for neutrophil count was assessed at baseline. Metabolite and exosomal signature (proteins and RNA) of drug resistance were also evaluated at different time points and will be reported separately. Primary endpoint was the proportion of patients who completed planned oncologic therapy without the development of a hematological event defined as episodes of febrile neutropenia (FN) or treatment discontinuation due to neutropenia. A two-stage design was used to test if the completion rate of planned oncologic therapy without a hematological event was at least 80% versus if it was below 60%, with 80% power at a significance level of 5%. Results: 35 women were enrolled from 5 different institutions. Mean age was 64 years (30-90). 9% (3/35) of patients had PS of 2. Visceral involvement was present in 51% (18/35) of patients; 60% (21/35) received an AI and 40% (14/35) received fulvestrant. Baseline median ANC was 3,100 (1,300-11,100) cells/mm3. None of the patients had FN or required discontinuation of therapy due to neutropenia. Grade 3 and 4 neutropenia were experienced by 46% (16/35) and 3% (1/35) of patients respectively. Dose delays occurred in 17 patients, and 13 patients required dose reduction (5 to 100mg and 8 to 75 mg). Clinical benefit rate (CR+PR+SD persisting for ≥6 months) was 70%. Of the 29 patients who have completed study participation, the median time on treatment was 280 days (14, 385) and 15 continued on commercial palbociclib. Last visit on study estimated for 10/2019. The Duffy polymorphism was evaluated in 94% (33/35) of patients. The Duffy null phenotype was present in 58% (19/33) of the patients. Lower baseline ANC (2,400 vs 4,300 cells/mm3, p0.006), grade 3 neutropenia (63.2 vs 21.4%, p0.003) and dose reductions (52.6 vs 7.1%, p0.009) were more common in patients with the Duffy null polymorphism. Conclusion: This is the first trial specifically designed to evaluate the hematologic toxicity of a CDK4/6i in AAW. Although patients with the Duffy null phenotype had more dose reductions and treatment delays due to neutropenia, this did not result in episodes of FN or treatment discontinuation due to neutropenia. This analysis suggests that palbociclib with ET is safe in AAW including those with the Duffy null phenotype. Citation Format: Filipa Lynce, Rebecca Zhuo, Matthew Blackburn, Christopher Gallagher, Olwen Hahn, Maysa Abu-Khalaf, Mahsa Mohebtash, Tianmin Wu, Paula Pohlmann, Asma Dilawari, Shruti Tiwari, Ami Chitalia, Robert Warren, Ming Tan, Ayesha Shajahan-Haq, Claudine Isaacs. Safety of palbociclib in African American women with hormone receptor positive HER2 negative advanced breast cancer and benign ethnic neutropenia: PALINA study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-20.

Relying on various defects and functional oxygen-containing groups on the basal planes, graphene oxide (GO) is commonly unitized for intimate mixing with a polymer matrix to fabricate high-performance nanocomposite polymeric materials with the characteristics of graphene. Herein, by introducing GO nanosheets in a phenanthraquinone-doped polymethyl methacrylate (PQ/PMMA) photopolymer, we demonstrate that the polarization holographic diffraction efficiency of nanocomposite materials can be dramatically enhanced up to nearly 10 times and the photosensitivity can also be enhanced by more than 3 times. Experimental observations reveal that the incorporation of GO nanosheets serves as a polymerization initiator not only to promote the polymerization of MMA monomers and induce the drafting behavior of the PMMA polymer on its surface but also to effectively modulate the molecular weight of the PQ/PMMA photopolymer by adjusting the doping concentration of GO nanosheets. The current study, for the first time, demonstrates that the modulation of molecular weight for PQ/PMMA photopolymers here exerts a significant impact on their holography performance. In addition, due to the strong physisorption of PQ photosensitizers onto GO nanosheets, the aggregation of PQ around GO-graft-PMMA also facilitates the formation of GO-graft-PMMA/PQ and is beneficial to the enhancement of holographic performance. The emergence of GO-graft-PMMA/PQ nanocomposite materials here is expected to fulfill the requirement of high-performance polarization-sensitive materials in the field of polarization holographic data storage and provide a facile but effective nanocomposite doping strategy to modulate the holographic performance of photopolymers from micro- and mesoscopic levels.

BackgroundTo investigate the effect of Ruanmailing oral liquid on atherosclerosis and TGF-β1/SMAD4 signaling pathway in ApoE knockout mice induced by high-fat diet. MethodsForty ApoE-/- mice were randomly divided into 5 groups, and mice fed with standard diets were the control group. ApoE-/- mice high-fat diet induced atherosclerotic phenotype. After grouping and treatment, they were divided into high-fat feeding model group, low-dose and high-dose of Ruanmailing groups (1.75, 4.55 ml/kg/d), Lipitor Group (3.0 mg/kg/d). After 12 weeks of administration, blood was collected from the mice orbit to determine the levels of TC, TG, LDL-C, and HDL-C, and the pathological changes of thoracic aorta atherosclerosis were observed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of serum TGF-β1, and RT-PCR and Western Blot were used to detect the expression of SMAD4 and GATA2 in the thoracic aorta of ApoE-/- mice in each group. ResultsCompared with the high-fat model group, the serum lipids level of each administration group were reduced (PPP-/- mice were alleviated, and the high-dose Ruanmailing group had the most significant anti-atherosclerotic effect. ConclusionsRuanmailing oral liquid has an anti-atherosclerotic effect, and its mechanism may be related to the intervention of GATA2 in the TGF-β1/SMAD4 signaling pathway to reduce the differentiation and proliferation of arterial smooth muscle cells.

Background: Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs. Methods: A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs. Results: The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non–small cell lung cancer, 45% (n=50) were treated using an anti–PD-(L)1 ICI, and 33% (n=37) were treated using an anti–PD-1/anti–CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs. Conclusions: Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.

Understanding the phonon transport in thermoelectric materials and its coupling with the complex environments is critical for manipulating the lattice thermal conductivity and consequently creating a high heat-to-electricity conversion efficiency. Spin-orbit coupling, an elementary interaction usually neglected when calculating lattice thermal conductivity, is intuitively expected to affect only the harmonic phonon properties in the materials. We herein studied the phonon transport in SnSe, a thermoelectric material with record-high energy conversion efficiency, by first-principle calculation and the Boltzmann transport equation. Spin-orbit coupling is found to greatly enhance its lattice thermal conductivity (up to ∼60%). More surprisingly, this enhancement originates from the influence of spin-orbit coupling on the phonon anharmonicity instead of the harmonic phonon properties. Spin-orbit coupling reduces the delocalization of the resonant bonding network formed by the p-orbitals of Se atoms, strengthens the interlayer Sn-Se bonds and consequently weakens the phonon anharmonicity. This discovery should encourage the design of tunable spin-orbit systems for better manipulation of thermoelectricity as well as other phonon transport related material functions.

There has been intense interest in hybrid organic-inorganic perovskites (HOIPs) in the materials science community due to their unexpected and fascinating properties with respect to photovoltaic applications. The intrinsic toxicity of Pb-based HOIPs, however, seriously hinders its practical large-scale commercialization. Exploring novel stable and environmentally friendly high-performance HOIPs for sunlight harvesting therefore becomes a scientific research hotspot in the photovoltaic research community. In contrast to devoting a great amount of effort to searching promising metal-cation-based HOIPs for photovoltaics, a comprehensive investigation of a series of silicon-based HOIPs is carried out in this study to discover metal-free high-performance HOIPs for photovoltaics. Remarkably, a new family of unexplored metal-free HOIPs with promising electronic properties for solar cells, theoretically confirmed to possess excellent thermal and environmental stability, is eventually discovered and expected to be tested for further experimental synthesis and characterization. The present study marks a significant step toward discovering a series of novel metal-free HOIPs for photovoltaics and provides novel cognition for rational design regarding eco-friendly and environmentally friendly materials.

Bilayer graphene possesses new degrees of freedom for modulating the electronic band structure, which makes it a tempting solution for overcoming the intrinsic absence of sizeable bandgaps in graphene and designing next-generation devices for post-silicon electronics. By twisting bilayer graphene, interlayer hybridized and twist angle-dependent van Hove singularities in the electronic band structure are generated and expected to facilitate the vertical tunneling transport between bilayer graphene. Herein, based on the ab initio quantum transport simulations, we designed a novel all-metallic vertical quantum transport architecture with the twisted bilayer graphene as the transport channel region and Au electrodes as the source/drain contacts to investigate the twist angle-dependent vertical transport properties. Enhancement in the ION/IOFF ratio by 2 orders of magnitude can be achieved by simply twisting the bilayer graphene. Compared to the traditional gate voltage modulation, which tunes the Fermi energy level alone, the current strategy shifts the Fermi energy level of the channel region away from the Dirac cone, moves the Fermi level and the van Hove singularities towards each other and promotes the vertical quantum transport due to the interlayer electronic hybridization. This dual modulation strategy of this novel mechanical gating device thus provides a potential new solution for designing novel vertical transistors.

GeSe is a IV-VI semiconductor, like the excellent thermoelectric materials PbTe and SnSe. Orthorhombic GeSe has been predicted theoretically to have good thermoelectric performance but is difficult to dope experimentally. Like PbTe, rhombohedral GeTe has a multivalley band structure, which is ideal for thermoelectrics and also promotes the formation of Ge vacancies to provide enough carriers for electrical transport. Herein, we investigate the thermoelectric properties of GeSe alloyed with AgSbSe2, which stabilizes a new rhombohedral structure with higher symmetry that leads to a multivalley Fermi surface and a dramatic increase in carrier concentration. The zT of GeAg0.2Sb0.2Se1.4 reaches 0.86 at 710 K, which is 18 times higher than that of pristine GeSe and over four times higher than doped orthorhombic GeSe. Our results open a new avenue towards developing novel thermoelectric materials via crystal phase engineering using a strategy of entropy stabilization of high symmetry alloys.

Two-dimensional transition-metal dichalcogenide semiconductors (TMDCs) such as MoS2 are attracting increasing interest as thermoelectric materials owing to their abundance, nontoxicity, and promising performance. Recently, we have successfully developed n-type MoS2 thermoelectric material via oxygen doping. Nevertheless, an efficient thermoelectric module requires both n-type and p-type materials with similar compatibility factors. Here, we present a facile approach to obtain a p-type MoS2 thermoelectric material with a maximum figure of merit of 0.18 through the introduction of VMo2S4 as a second phase by vanadium doping. VMo2S4 nanoinclusions, confirmed by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) measurements, not only improve the electrical conductivity by simultaneously increasing the carrier concentration and the mobility but also result in the reduction of lattice thermal conductivity by enhancing the interface phonon scattering. Our studies not only shed new light t...

We review in this article our recent simulation works on modeling peptide T-jump and thermal unfolding Fourier transform infrared spectroscopy (FTIR) and two-dimensional infrared (2DIR) spectra. The theoretical and computational techniques used, including Markov state model (MSM), integrated tempering sampling (ITS) and nonlinear exciton propagation (NEP), are first briefly introduced. The protocols for simulating the thermal unfolding as well as T-jump unfolding are then summarized in details. The simulated spectral features, such as the intensity and ellipticity, are demonstrated to agree well with the experimental observations.

Two-dimensional transition-metal dichalcogenide semiconductors (TMDCs) with layered structures, such as MoS2, hold great potential to become economic and nontoxic thermoelectric materials. Application of TMDCs is hampered, however, by their insignificant power factors which cancel the advantage of their intrinsically low thermal conductivities along the cross-plane direction and lead to less satisfactory overall thermoelectric performances. Here we report that, by adopting an oxygen doping strategy, the thermoelectric efficiency of MoS2 can be enhanced up to 50 times with the best performance appearing along the cross-plane direction. Our further characterization suggests that this plausible improvement originates from the MoO2 nanoinclusions, which enhance the electrical conductivity and Seebeck coefficient, while suppressing the thermal conductivity at the same time. The unexpected simultaneous enhancement of the electrical conductivity and Seebeck coefficient after doping is explained using an electron relaxation time model. We therefore provide a general strategy towards improving the thermoelectric performance of TMDCs.

Van der Waals heterostructures composed of two-dimensional transition-metal dichalcogenides layers have recently emerged as a new family of materials, with great potential for atomically thin opto-electronic and photovoltaic applications. It is puzzling, however, that the photocurrent is yielded so efficiently in these structures, despite the apparent momentum mismatch between the intralayer/interlayer excitons during the charge transfer, as well as the tightly bound nature of the excitons in 2D geometry. Using the energy-state-resolved ultrafast visible/infrared microspectroscopy, we herein obtain unambiguous experimental evidence of the charge transfer intermediate state with excess energy, during the transition from an intralayer exciton to an interlayer exciton at the interface of a WS2/MoS2 heterostructure, and free carriers moving across the interface much faster than recombining into the intralayer excitons. The observations therefore explain how the remarkable charge transfer rate and photocurrent generation are achieved even with the aforementioned momentum mismatch and excitonic localization in 2D heterostructures and devices., Van der Waals heterostructures, fabricated via vertical stacking of two-dimensional materials, hold promise for opto-electronic applications. Here, the authors study the exciton-assisted charge transfer mechanisms occurring in a WS2/MoS2 heterojunction via ultrafast microspectroscopy.

In integrative analysis parametric or nonparametric methods are often used. The former is easier for interpretation but not robust, while the latter is robust but not easy to interpret the relationships among the different types of variables. To combine the advantages of both methods and for flexibility, here a system of semiparametric projection non-linear regression models is proposed for the integrative analysis, to model the innate coordinate structure of these different types of data, and a diagnostic tool is constructed to classify new subjects to the case or control group. Simulation studies are conducted to evaluate the performance of the proposed method, and shows promising results. Then the method is applied to analyze a real omics data from The Cancer Genome Atlas study, compared the results with those from the similarity network fusion, another integrative analysis method, and results from our method are more reasonable.

Thermoelectric power generators, as one promising renewable energy resource, have attracted intense attention over the past few decades. However, the large-scale use of thermoelectric convertors relies on cost-effective and eco-friendly thermoelectric materials with decent efficiency. For transition metal dichalcogenide semiconductors (TMDCs), a potential thermoelectric material, their thermoelectric efficiency is hampered by their poor intrinsic electrical conductivities. Herein, we demonstrate that the thermoelectric performance of WS2, a typical TMDC material, can be dramatically enhanced by up to 70 times by doping with titanium. The anisotropic thermoelectric properties of these layered WS2 structures were also systematically revealed. The realization of decent thermoelectric efficiency of WS2 by a facile doping strategy will stimulate future explorations of thermoelectric applications for other TMDCs and layered materials.

Traditional trial-and-error methods seriously restrict and hinder the searching of high-performance functional materials, especially when the search space is large. Rapid searching for advanced functional materials has always been a hot research topic, and attracted a lot of experimental and theoretical research attention. Here, by combining machine learning method with density functional theory (DFT) calculations, a target-driven method is proposed here to speed up the discovery of hidden hybrid organic-inorganic perovskites (HOIPs) for photovoltaic applications from 230808 HOIPs candidates which is almost two orders larger than previous studied. After imposing two criterions, i.e., charge neutrality condition and stability condition, on potential HOIPs candidates, followed by a machine learning (ML) screening, 686 orthorhombic-like HOIPs with proper bandgap are selected. In machine learning screening, ensemble learning using three ML models, including gradient boosting regression (GBR), supporting vector regression (SVR) and kernel ridge regression (KRR), are applied to predict the bandgap of 38086 HOIPs candidates. 132 stable and non-toxic (Cd-, Pb- and Hg-free) orthorhombic-like HOIPs are finally verified by DFT calculations with appropriate band gap for solar cells. In the present study, not only a series of unexplored stable and non-toxic HOIPs are discovered for further experimental synthesis, a new HOIPs database is constructed as well, thus beneficial to future functional material design.

Introduction: Patients (pts) with high-risk multiple myeloma (HRMM) experience early disease progression post autologous stem cell transplant (ASCT). The median progression free survival (PFS) for HRMM pts undergoing ASCT with lenalidomide (len) maintenance ranges between 27 and 42 months in high risk pts and 22 months in ultra-high risk, defined by two or more adverse cytogenetic abnormalities such as: gain(1q), t(4;14), t(14;16),t(14;20), or del(17p)( Chakraborty et al, Leukemia,2018 and Jackson et al, Lancet, 2018). Elotuzumab, a humanized IgG kappa monoclonal antibody against SLAM-F7 (CS-1), is approved in combination with len and dexamethasone (ERd) in pts with relapsed MM (Dimopoulus et al, BJH, 2017). It directly activates natural killer (NK) cells and mediates myeloma cell death by antibody-dependent cell mediated cytoxicity. We hypothesized that administration of ERd as post-ASCT consolidation will enhance an immune-competent phenotype, by restoring NK cells and effector T-cell populations at a time of maximal disease de-bulking, and will ultimately improve outcomes among pts with HRMM. Methods: Thirty-one HRMM patients who achieved stable disease or better were treated beginning at 30-90 days post ASCT with ERd (29/31 pts) or elotuzumab/pomalidomide )/dex (EPd) (2/31 pts) between September 2016 and February 2019. With institutional review board approval, electronic medical records were reviewed for baseline characteristics, treatment history, adverse events (AE) while on therapy as defined by common terminology criteria for adverse events (CTCAE), and survival outcomes. Treatment with ERd or EPd was administered for 4 consecutive 28-day cycles per standard dosing regimens with a tapering or discontinuation of corticosteroids per investigator discretion with cycles 3 and 4. HRMM was defined by any of the following: ISS or Revised-ISS stage 3, CD-138 selected FISH with del 17p, 1q21 gain, t(4;14), t(14;16), and t(14;20), cytogenetics with 13q del or complex karyotype, and/or high-risk gene expression profile score. Ultra-HR pts were defined by having both del 13q and 1q21 gain by FISH based on recent unpublished COMPASS data. Minimal residual disease (MRD) was evaluated upon achievement of very good partial remission or complete remission using 10-color multiparametric flow cytometry. PFS was measured using the log-rank test. Response criteria was defined per International Myeloma Working Group criteria. Results: Baseline characteristics of all 31 patients are shown in Table 1. Thirty-four percent were ISS-3, 71% (22/31 pts) had high-risk FISH, of which 19% were ultra-high risk (6/22 pts). Seven pts (22.6%) underwent tandem-ASCT pre-consolidation. Of the 8 pts who had GEP testing, 2 (25%) were high risk. Best response to treatment by cycle is depicted in Table 2. Consolidative ERd/EPd deepened response compared to post-ASCT with 71.4% vs 19.4% achieving stringent complete remission (sCR). Post-consolidation, 19.3% vs 12.9%, pre-consolidation, achieved MRD negativity. With a median follow-up of 24.8 months, median PFS was 31.4 months (Figure 1). There was no significant association between median PFS and variables such as tandem ASCT and ultra-HR using multivariate cox regression. Although all pts experienced at least one AE while on therapy, only 1 patient (3.22%) experienced a grade 3 AE. Hematologic AEs included: anemia (48%), neutropenia (45%), and thrombocytopenia (52%), while the most common non-hematologic AEs included: fatigue (32%), malaise (23%), and back pain (19%). One patient experienced a serious AE (SAE) which was PCP pneumonia requiring hospitalization, resulting in early discontinuation from therapy. There was no treatment-related mortality. Conclusion: ERd or EPd as 4 months of fixed duration consolidation therapy post-ASCT resulted in a median PFS of 31.4 months amongst pts with HRMM, similar to or perhaps surpassing historical reports of HRMM pts receiving lenalidomide maintenance until progression. This therapy may offer comparable, if not superior, outcomes while having the advantage of allowing for significant time without therapy and perhaps improving quality of life and financial toxicity. This study is limited due to its retrospective nature. Larger prospective studies evaluating fixed duration ERd/EPd in HRMM patients post ASCT should be conducted. Disclosures Rowley: Allergan: Equity Ownership; Fate Therapeutics: Consultancy. Goldberg:COTA: Equity Ownership; Bristol-Myers Squibb: Consultancy; Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership. Siegel:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Biran:Bristol Meyers Squibb: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Merck: Research Funding.

Stirnemann et al. (1) argue that the general deceleration of water reorientation dynamics in the concentrated electrolytes is not entirely due to the frame retardation, since suppressing frame reorientation entirely leads to a maximum slowdown of 1 τ r e o r j u m p + 1 τ r e o r f r a m e 1 τ r e o r j u m p ≈ 1.6 , smaller than the deceleration in many concentrated electrolytes. This same argument, however, can be used to reason that the general deceleration does not entirely come from the retarded jump either, since the decelerations in many concentrated electrolytes are larger than 1 τ r e o r j u m p + 1 τ r e o r f r a m e 1 τ r e o … [↵][1]1To whom correspondence may be addressed. Email: smukamel{at}uci.edu or wzhuang{at}fjirsm.ac.cn. [1]: #xref-corresp-1-1

Water dynamics in concentrated ionic solutions plays an important role in a number of material and energy conversion processes such as the charge transfer at the electrolyte-electrode interface in aqueous rechargeable ion batteries. One long-standing puzzle is that all electrolytes, regardless of their "structure-making/breaking" nature, make water rotate slower at high concentrations. To understand this effect, we present a theoretical simulation study of the reorientational motion of water molecules in different ionic solutions. Using an extended Ivanov model, water rotation is decomposed into contributions from large-amplitude angular jumps and a slower frame motion which was studied in a coarse-grained manner. Bearing a certain resemblance to water rotation near large biological molecules, the general deceleration is found to be largely due to the coupling of the slow, collective component of water rotation with the motion of large hydrated ion clusters ubiquitously existing in the concentrated ionic solutions. This finding is at variance with the intuitive expectation that the slowing down is caused by the change in fast, single-molecular water hydrogen bond switching adjacent to the ions.

Two-dimensional transition-metal dichalcogenide semiconductors (TMDCs) such as MoS

Using a molecular dynamics simulation technique, we compared several commonly used ion-water models to describe the microscopic structures and dynamics in KSCN aqueous solutions. Results are compared with observations of femtosecond infrared vibrational-energy transfer and anisotropy measurements. The Jorgensen/TIP4P model is found to provide the best reproduction of clustering properties such as percentage of clustered ions, cluster-size distribution, concentration dependence of the water, and ion-rotation time constants.

Water rotational dynamics in NaSCN and KSCN solutions at a series of concentrations are investigated using femtosecond infrared spectroscopy and theory., Water rotational dynamics in NaSCN and KSCN solutions at a series of concentrations are investigated using femtosecond infrared spectroscopy and theory. Femtosecond infrared measurements, consistent with previous NMR observations, detect that sodium slows down while potassium accelerates the water O–H bond rotation. Results of reported neutron scattering measurements, on the other hand, suggested that these two cations have similar structure-breaking effects on water, and therefore should both accelerate water rotation through the presumably dominating large-amplitude angular jump component. To explain this discrepancy, theoretical studies with both classical and ab initio models were carried out, which indicate that both ions indeed accelerate the large-amplitude angular jump rotation of the water molecules, while the observed cation specific effect originates from the non-negligible opposite impact of the sodium and potassium cations on the diffusive rotation of water molecules.

Phase transitions of electron-hole pairs on semiconductor/conductor interfaces determine fundamental properties of optoelectronics. To investigate interfacial dynamical transitions of charged quasiparticles, however, remains a grand challenge. By employing ultrafast mid-infrared microspectroscopic probes to detect excitonic internal quantum transitions and two-dimensional atomic device fabrications, we are able to directly monitor the interplay between free carriers and insulating interlayer excitons between two atomic layers. Our observations reveal unexpected ultrafast formation of tightly bound interlayer excitons between conducting graphene and semiconducting MoSe

In this work, MD simulations with two different force fields, vibrational energy relaxation and resonant energy transfer experiments, and neutron scattering data are used to investigate ion pairing and clustering in a series of GdmSCN aqueous solutions. The MD simulations reproduce the major features of neutron scattering experimental data very well. Although no information about ion pairing or clustering can be obtained from the neutron scattering data, MD calculations clearly demonstrate that substantial amounts of ion pairs and small ion clusters (subnanometers to a few nanometers) do exist in the solutions of concentrations 0.5 M*, 3 M*, and 5 M* (M* denotes mole of GdmSCN per 55.55 mole of water). Vibrational relaxation experiments suggest that significant amounts of ion pairs form in the solutions. Experiments measuring the resonant energy transfers among the thiocyanate anions in the solutions suggest that the ions form clusters and in the clusters the average anion distance is 5.6 Å (5.4 Å) in the 3 M* (5 M*) Gdm-DSCN/D2O solution.