Compassionate Use of Remdesivir in Pregnancy: A Case Series From a COVID-19 Dedicated Center and Review of Literature.

Pregnancy is associated with immunological changes that could render an individual vulnerable to the severe coronavirus disease 2019 (COVID-19) disease. Even as we witnessed the third and most widespread pandemic wave, a conclusively advantageous treatment option still remained elusive. Remdesivir was one of the front-running therapeutic options that received emergency use authorization (EUA) and subsequent approval for the management of moderate to severe COVID-19 infections. Here, we report a series of moderate to severe COVID-19-infected pregnancies and the experience of remdesivir use on a compassionate basis. Four cases of pregnancy complicated with moderate to severe COVID-19 infections where remdesivir was administered were recruited into the study, and their outcome was assessed objectively. Of these cases, three women received remdesivir in addition to standard SARS-CoV-2 treatment in the antenatal period. One woman received remdesivir after delivery. One woman received tocilizumab in addition to remdesivir and standard SARS-CoV-2 care. Two women survived and were subsequently discharged to home care. Two succumbed to the disease. One baby who was exposed to remdesivir in utero is doing well at six months post-delivery. Remdesivir had been granted EUA for the treatment of suspected or laboratory-confirmed COVID-19 infection in adults and children who were hospitalized with severe disease or requiring supplemental oxygen and mechanical ventilation or extracorporeal membrane oxygenation (ECMO) in May 2020. This issuance allowed the use of the same dosing regimen in pregnant and parturient women as in the general adult population. Thus, this series of cases tried to assess the outcome of this drug among COVID-19-infected pregnant women. Early initiation of remdesivir in pregnancy in the viremic phase seems to provide some advantages in the survival outcome. Its use may be associated with transient elevation in hepatic transaminases in some cases. No detrimental effects on the ongoing pregnancies, fetuses, or neonates have been observed. Further large-scale studies may provide more conclusive evidence.

Application of a Negative Intrauterine Pressure Suction Device for Prophylactic Management of Atonic Postpartum Hemorrhage: A Quality Improvement Study.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide. PPH-preventing interventions need to be prioritized and can be integrated with conventional methods of PPH prevention. The introduction of negative intrauterine pressure using a suction cannula can be one of the cheapest modalities to decrease PPH secondary to uterine atonicity. This method has brought a renaissance to practical obstetrics in low-middle income countries (LMIC), where the cost and availability of uterotonics are major health issues. METHODS: It was a prospective quality improvement (QI) study conducted in the labor and delivery wards of a tertiary care medical institute and teaching center over the duration of one year. We aimed to assess the decrease in the incidence of atonic PPH with a negative intrauterine pressure suction device (NIPSD) integrated with active management of the third stage of labor (AMTSL) in the prevention of atonic PPH following normal vaginal delivery in low-risk antenatal women. In the initial six months, routine AMTSL was instituted for all consenting women (group 1). In the next six months, NIPSD was integrated with AMTSL (group 2). Data pertaining to the amount of blood loss, the incidence of primary PPH, uterine tone, fall in hemoglobin and hematocrit levels post-delivery, need for blood transfusion, and doctor and patient satisfaction were tabulated for all patients. RESULTS: A total of 1324 consenting women were eligible for enrollment during the study time frame. In the initial six months (baseline period, group 1), 715 participants were subjected to routine AMTSL in the third stage of labor. During the intervention phase (group 2), 609 parturient women were recruited. There was no significant difference in baseline parameters between the two groups. With the introduction of NIPSD to routine AMTSL, there was a significant decrease in the average volume of blood loss during vaginal delivery (group 1 = 389.45+65.42 ml, group 2 = 216.66+34.27 ml; p-value = 0.012). The incidence of atonic PPH was reduced by more than 75% (group 1 = 13 women, group 2 = 3 women; p-value = 0.001) after the introduction of NIPSD complementing routine AMTSL. The introduction of NIPSD has also been instrumental in reducing the cost burden on patient and hospital expenditures. The net benefit of its introduction resulted in a reduction of the overall cost burden of blood transfusions by around 70%. CONCLUSION: PPH is a public health problem, and measures to reduce PPH must be implemented to decrease this health burden. In countries with low resources, complementing routine AMTSL with NIPSD can be instrumental in decreasing the incidence of PPH. Considering its cost-effectiveness and reusability, LMIC can adopt NIPSD as a routine measure in all vaginal deliveries.

Status of Contraceptive Use for Birth Spacing After a Teenage Pregnancy: Where Do We Stand?

BACKGROUND: Adolescence is the most complex stage of reproductive health. The knowledge and awareness of adolescent-related reproductive issues are limited, particularly in lower-middle-income countries. Adolescent pregnancies are associated with major maternal and neonatal complications. Effective contraception use can prevent teenage pregnancy and subsequent complications. METHODS: It was a cross-sectional study conducted in a tertiary care hospital and teaching institute over a period of one year. Through this study, we aimed to assess the prevalence of postpartum use of approved standard methods of contraception for birth spacing among teenage mothers and to assess the reasons for their non-acceptance. A total of 133 consecutive consenting postpartum teenage mothers were recruited in the study. Participants were asked about their age at the time of marriage and delivery, marital status, parity, education and economic status, the number of antenatal visits, mode of delivery, and antenatal complications. Compliance with postpartum contraception was noted, and reasons for its non-acceptance were asked in detail. RESULTS: Among the 133 participants, contraceptive users were categorized into Group A and non-users into Group B. The mean age at the time of marriage was 17.6±0.4 and 17.5±0.6 years in Group A and Group B, respectively. Mothers in Group A were more educated than their counterparts in Group B (82.2% of mothers were educated up to 12th standard in Group A compared to 46.6% in Group B). Among the contraception users, 70% had four or more antenatal visits compared to 7.9% of the non-users. Reasons for non-acceptance of postpartum contraception were elicited in Group B: 42.0% had fear of becoming infertile, 38.6% feared that contraceptives interfere with breastfeeding and quality of breastmilk, 13.6% had opposition from family members, and 5.8% did not mention any reason. CONCLUSION: Teenage pregnancy is associated with increased feto-maternal complications. It also accounts for an increased incidence of unsafe abortions and maternal mortality. So it is crucial to make the adolescent group aware of effective methods of postpartum contraceptives to prevent adolescent pregnancies. Collaborative larger multicentric studies from different countries will help to reach a better, generalized conclusion regarding the same.

Assessment of Fertility Outcomes Following Combined Clomiphene and Letrozole Versus Letrozole Therapy for the Treatment of Polycystic Ovarian Syndrome Subfertility.

BACKGROUND: Poly Cystic Ovarian Syndrome (PCOS) affects 8-13% of women in their reproductive age and is one of the foremost causes of female subfertility. Traditionally, clomiphene citrate has been the first-line treatment for ovulation induction in PCOS. However, the European Society of Human Reproduction and Embryology (ESHRE) international evidence-based guidelines in 2018 recommended the use of letrozole as first-line therapy for ovulation induction in anovulatory PCOS women, due to better pregnancy and live birth rates. Here we aimed to evaluate the effect of combined - clomiphene and letrozole versus letrozole for the treatment of PCOS subfertility. METHODS: It was a retrospective cohort study conducted on reproductive-age women fulfilling Rotterdam Criteria for PCOS with a history of subfertility. All participants receiving at least one cycle of letrozole and clomiphene combination were recruited as cases. However, women receiving letrozole only for ovulation induction were taken as controls. Hospital records were abstracted for data on baseline characteristics such as age, duration of infertility, PCOS phenotype, body mass index (BMI), past medical and fertility history, treatment with ovulation induction agents, and metformin use. The mean size of the largest follicle, number of dominant follicles of size greater than 15 mm and endometrial thickness on Days 12-14 or on the day of the luteinizing hormone (LH) surge were recorded. A cycle was termed ovulatory if serum progesterone levels were > 5.0 ng/ml on the seventh day after the LH surge or day 22 in the absence of the LH surge. Data pertaining to therapy-associated side effects were also abstracted from the clinical records. RESULTS: Amongst the ovulatory cycles in both groups, there was no significant difference in the day of the LH surge. Serum progesterone levels on the seventh day post-ovulation were higher with combination therapy (19.35 v/s 26.71, p=0.004). The number of ovulatory cycles was also greater with combination therapy, but the difference was just short of significant (25 vs 18, p=0.08). The mean diameter of the largest follicle, incidence of multi-follicular ovulation, and thin endometrium were similar in both groups. The adverse effect profile was similar in both groups. CONCLUSION: Combination treatment of clomiphene citrate with letrozole may potentially improve fertility outcomes in PCOS subfertility in terms of the likelihood of ovulation and higher post-ovulatory progesterone levels, however, larger studies are required.

Parkin ubiquitination of Kindlin-2 enables mitochondria-associated metastasis suppression.

Mitochondria are signaling organelles implicated in cancer, but the mechanisms are elusive. Here, we show that Parkin, an E3 ubiquitination (Ub) ligase altered in Parkinson's disease, forms a complex with the regulator of cell motility, Kindlin-2 (K2), at mitochondria of tumor cells. In turn, Parkin ubiquitinates Lys581 and Lys582 using Lys48 linkages, resulting in proteasomal degradation of K2 and shortened half-life from ∼5 h to ∼1.5 h. Loss of K2 inhibits focal adhesion turnover and ß1 integrin activation, impairs membrane lamellipodia size and frequency, and inhibits mitochondrial dynamics, altogether suppressing tumor cell-extracellular matrix interactions, migration, and invasion. Conversely, Parkin does not affect tumor cell proliferation, cell cycle transitions, or apoptosis. Expression of a Parkin Ub-resistant K2 Lys581Ala/Lys582Ala double mutant is sufficient to restore membrane lamellipodia dynamics, correct mitochondrial fusion/fission, and preserve single-cell migration and invasion. In a 3D model of mammary gland developmental morphogenesis, impaired K2 Ub drives multiple oncogenic traits of EMT, increased cell proliferation, reduced apoptosis, and disrupted basal-apical polarity. Therefore, deregulated K2 is a potent oncogene, and its Ub by Parkin enables mitochondria-associated metastasis suppression.

Intercellular hif1α reprograms mammary progenitors and myeloid immune evasion to drive high-risk breast lesions.

The origin of breast cancer, whether primary or recurrent, is unknown. Here, we show that invasive breast cancer cells exposed to hypoxia release small extracellular vesicles (sEVs) that disrupt the differentiation of normal mammary epithelia, expand stem and luminal progenitor cells, and induce atypical ductal hyperplasia and intraepithelial neoplasia. This was accompanied by systemic immunosuppression with increased myeloid cell release of the alarmin S100A9 and oncogenic traits of epithelial-mesenchymal transition, angiogenesis, and local and disseminated luminal cell invasion in vivo. In the presence of a mammary gland driver oncogene (MMTV-PyMT), hypoxic sEVs accelerated bilateral breast cancer onset and progression. Mechanistically, genetic or pharmacologic targeting of hypoxia-inducible factor-1α (HIF1α) packaged in hypoxic sEVs or homozygous deletion of S100A9 normalized mammary gland differentiation, restored T cell function, and prevented atypical hyperplasia. The transcriptome of sEV-induced mammary gland lesions resembled luminal breast cancer, and detection of HIF1α in plasma circulating sEVs from luminal breast cancer patients correlated with disease recurrence. Therefore, sEV-HIF1α signaling drives both local and systemic mechanisms of mammary gland transformation at high risk for evolution to multifocal breast cancer. This pathway may provide a readily accessible biomarker of luminal breast cancer progression.

Assessment of Risk Factors and Obstetric Outcome of Adolescent Pregnancies Through a Prospective Observational Analysis.

Background Adolescence is the most crucial stage of life. Early marriage and teenage pregnancy infringe on adolescent girls' social and humanitarian rights. Moreover, it leads to school dropouts and decreased self-autonomy. Through this study, we aimed to analyze the risk factors and obstetric and neonatal outcomes resulting from adolescent pregnancies conceived by Indian girls less than 20 years of age. Materials and methods It was a prospective observational study conducted over a period of two years. Consecutive consenting adolescent mothers visiting the antenatal clinic or the delivery wards were recruited into the study. Adolescent pregnancies constituted all pregnancies where the maternal age was between 14 and 19 years at the time of presentation. Participants were followed prospectively till delivery and postpartum visit at six weeks to assess the obstetric and puerperal outcomes. Treating obstetricians asked about the causes responsible for current teenage pregnancy. At the time of delivery, data pertaining to antenatal complications, pregnancy outcome, mode of delivery, and birth weight were noted. All women were counseled for postpartum contraception at the time of delivery. Compliance with postpartum contraception was noted, and reasons for non-acceptance were asked. Results A total of 133 antenatal women in the adolescent age group were recruited during the study time frame. The mean age at the time of delivery was 18.4 years. Most of the women were educated between the sixth and 12th standards and belonged to the upper-lower economic class. Early marriage, increased family pressure, and school dropout at a young age were the predominant risk factors for teenage pregnancy in the study population. The majority of them suffered from anemia. Pregnancy-induced hypertension, hypothyroidism, fetal growth restriction, and oligohydramnios were a few other complications seen in adolescent pregnancies. Despite counseling, only 33.8% of adolescent mothers accepted postpartum contraception (any of the standard methods). Conclusion Pregnancy has concerning health consequences on adolescent girls and their babies. For example, adolescent mothers face increased risks of pregnancy-induced hypertension, obstructed labor, and puerperal sepsis. So, it is time to create awareness through mass educational campaigns and widespread family planning services.

Mitochondrial fitness and cancer risk.

Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal tissues, and correlates with poor patient outcome. When analyzed in three independent patient cohorts of pancreatic ductal adenocarcinoma (PDAC), the Mic60-low gene signature was associated with aggressive disease variants, local inflammation, FOLFIRINOX failure and shortened survival, independently of age, gender, or stage. Therefore, the 11-gene Mic60-low signature may provide an easily accessible molecular tool to stratify patient risk in PDAC and potentially other malignancies.

NFκB activation by hypoxic small extracellular vesicles drives oncogenic reprogramming in a breast cancer microenvironment.

Small extracellular vesicles (sEV) contribute to the crosstalk between tumor cells and stroma, but the underlying signals are elusive. Here, we show that sEV generated by breast cancer cells in hypoxic (sEVHYP), but not normoxic (sEVNORM) conditions activate NFκB in recipient normal mammary epithelial cells. This increases the production and release of inflammatory cytokines, promotes mitochondrial dynamics leading to heightened cell motility and disrupts 3D mammary acini architecture with aberrant cell proliferation, reduced apoptosis and EMT. Mechanistically, Integrin-Linked Kinase packaged in sEVHYP via HIF1α is sufficient to activate NFκB in the normal mammary epithelium, in vivo. Therefore, sEVHYP activation of NFκB drives multiple oncogenic steps of inflammation, mitochondrial dynamics, and mammary gland morphogenesis in a breast cancer microenvironment.

Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability.

Cancer metabolism, including in mitochondria, is a disease hallmark and therapeutic target, but its regulation is poorly understood. Here, we show that many human tumors have heterogeneous and often reduced levels of Mic60, or Mitofilin, an essential scaffold of mitochondrial structure. Despite a catastrophic collapse of mitochondrial integrity, loss of bioenergetics, and oxidative damage, tumors with Mic60 depletion slow down cell proliferation, evade cell death, and activate a nuclear gene expression program of innate immunity and cytokine/chemokine signaling. In turn, this induces epithelial-mesenchymal transition (EMT), activates tumor cell movements through exaggerated mitochondrial dynamics, and promotes metastatic dissemination in vivo. In a small-molecule drug screen, compensatory activation of stress response (GCN2) and survival (Akt) signaling maintains the viability of Mic60-low tumors and provides a selective therapeutic vulnerability. These data demonstrate that acutely damaged, "ghost" mitochondria drive tumor progression and expose an actionable therapeutic target in metastasis-prone cancers.

Laparoscopic Sacrocervicopexy Using Ethibond Suture Graft: A Very Economic Yet Effective Fertility Preserving Surgery for Pelvic Organ Prolapse.

BACKGROUND: The modern era has witnessed a transition to a phase of uterus-preserving surgeries and so holds true for pelvic organ prolapse (POP) surgeries as well. Laparoscopic sacrocervicopexy has become a preferred surgical modality for moderate to severe degrees of POP in most women of the childbearing age group. With the alarming incidences of mesh erosion, synthetic mesh has almost gone off the market. We advocate a very simple and cost-effective technique of laparoscopic sacrocervicopexy using an Ethibond suture graft. MATERIALS AND METHODS: It was a pilot prospective observational study over one year. Consecutive consenting women with symptomatic prolapsed uterus Stage-II of the central component of the quantitative POP classification (POP-Q) were recruited. Laparoscopic sacrocervicopexy was performed under general anesthesia using the standard protocols, and patients were prospectively followed for six months after surgery. The duration of surgery and hospital stay were noted. Patient satisfaction was rated using a five-point Likert scale. The vaginal length was measured immediately after and six months post-surgery. Sexual function was assessed using the validated female sexual function index (FSFI) scale six months after sacrocervicopexy. RESULTS: Out of 28 recruited women, the majority were multiparous, highly qualified, and belonged to the middle socio-economic class. Seven patients had co-morbidity in the form of hypertension (17.8%), diabetes (7.1%), and cardiovascular diseases (7.1%). The mean duration of surgery was 105.8±7.2 minutes in the study population. The mean duration of hospital stay was 2.2±0.6 days. No surgical site infection was noted in any of the cases. Most patients rated "very satisfied" experiences following surgery (67.9%). The mean vaginal length after surgery was 7.6±1.2 centimeters. After a follow-up period of six months, the mean vaginal length was 7.4±0.8 centimeters. The mean FSFI score was 30.8±2.4. CONCLUSION: Laparoscopic sacrocervicopexy with Ethibond suture graft is a cost-effective and safe surgical technique for POP in resource-limited settings. It also obviates the additional cost of synthetic mesh and the long-term risks of mesh erosion.

A cancer ubiquitome landscape identifies metabolic reprogramming as target of Parkin tumor suppression.

Changes in metabolism that affect mitochondrial and glycolytic networks are hallmarks of cancer, but their impact in disease is still elusive. Using global proteomics and ubiquitome screens, we now show that Parkin, an E3 ubiquitin ligase and key effector of mitophagy altered in Parkinson's disease, shuts off mitochondrial dynamics and inhibits the non-oxidative phase of the pentose phosphate pathway. This blocks tumor cell movements, creates metabolic and oxidative stress, and inhibits primary and metastatic tumor growth. Uniformly down-regulated in cancer patients, Parkin tumor suppression requires its E3 ligase function, is reversed by antioxidants, and is independent of mitophagy. These data demonstrate that cancer metabolic networks are potent oncogenes directly targeted by endogenous tumor suppression.

Role of defects and grain boundaries in the thermal response of wafer-scale hBN films.

With more widespread applications of nanotechnology, heat dissipation in nanoscale devices is becoming a critical issue. We study the thermal response of wafer-scale hexagonal boron nitride (hBN) layers, which find potential applications as ideal substrates in two dimensional devices. Sapphire-supported thin hBN films, 2'' in size and of different thicknesses, were grown using metalorganic vapour phase epitaxy. These large-scale films exhibit wrinkles defects and grain boundaries over their entire area. The shift of [Formula: see text] phonon mode with temperature is analysed by considering the cumulative contribution of anharmonic phonon decay along with lattice thermal expansion, defect, and strain modulation. The study demonstrates that during heat treatment the strain evolution plays a dominating role in governing the characteristics of the wrinkled thinner films. Interestingly we find that both defects and strain determine the spectral line-width of these wafer-scale films. To the end, from Raman line-width, the changes in phonon lifetime in delaminated and as-grown films is estimated. The results suggest the possibility of a reduction in thermal transport in these wafer-scale films compared to their bulk counterpart.

Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment.

The crosstalk between tumor cells and the adjacent normal epithelium contributes to cancer progression, but its regulators have remained elusive. Here, we show that breast cancer cells maintained in hypoxia release small extracellular vesicles (sEVs) that activate mitochondrial dynamics, stimulate mitochondrial movements, and promote organelle accumulation at the cortical cytoskeleton in normal mammary epithelial cells. This results in AKT serine/threonine kinase (Akt) activation, membrane focal adhesion turnover, and increased epithelial cell migration. RNA sequencing profiling identified integrin-linked kinase (ILK) as the most upregulated pathway in sEV-treated epithelial cells, and genetic or pharmacologic targeting of ILK reversed mitochondrial reprogramming and suppressed sEV-induced cell movements. In a three-dimensional (3D) model of mammary gland morphogenesis, sEV treatment induced hallmarks of malignant transformation, with deregulated cell death and/or cell proliferation, loss of apical-basal polarity, and appearance of epithelial-to-mesenchymal transition (EMT) markers. Therefore, sEVs released by hypoxic breast cancer cells reprogram mitochondrial dynamics and induce oncogenic changes in a normal mammary epithelium.

The mitophagy effector FUNDC1 controls mitochondrial reprogramming and cellular plasticity in cancer cells.

Mitochondria are signaling hubs in eukaryotic cells. Here, we showed that the mitochondrial FUN14 domain-containing protein-1 (FUNDC1), an effector of Parkin-independent mitophagy, also participates in cellular plasticity by sustaining oxidative bioenergetics, buffering ROS production, and supporting cell proliferation. Targeting this pathway in cancer cells suppressed tumor growth but rendered transformed cells more motile and invasive in a manner dependent on ROS-mediated mitochondrial dynamics and mitochondrial repositioning to the cortical cytoskeleton. Global metabolomics and proteomics profiling identified a FUNDC1 interactome at the mitochondrial inner membrane, comprising the AAA+ protease, LonP1, and subunits of oxidative phosphorylation, complex V (ATP synthase). Independently of its previously identified role in mitophagy, FUNDC1 enabled LonP1 proteostasis, which in turn preserved complex V function and decreased ROS generation. Therefore, mitochondrial reprogramming by a FUNDC1-LonP1 axis controls tumor cell plasticity by switching between proliferative and invasive states in cancer.

IDH2 reprograms mitochondrial dynamics in cancer through a HIF-1α-regulated pseudohypoxic state.

The role of mitochondria in cancer continues to be debated and paradoxically implicated in opposing functions in tumor growth and tumor suppression. To understand this dichotomy, we explored the function of mitochondrial isocitrate dehydrogenase (IDH)2, a tricarboxylic acid cycle enzyme mutated in subsets of acute leukemias and gliomas, in cancer. Silencing of IDH2 in prostate cancer cells impaired oxidative bioenergetics, elevated reactive oxygen species (ROS) production, and promoted exaggerated mitochondrial dynamics. This was associated with increased subcellular mitochondrial trafficking, turnover of membrane focal adhesion complexes, and enhanced tumor cell migration and invasion, without changes in cell cycle progression. Mechanistically, loss of IDH2 caused ROS-dependent stabilization of hypoxia-inducible factor-1α in normoxia, which was required for increased mitochondrial trafficking and tumor cell movements. Therefore, IDH2 is a dual regulator of cancer bioenergetics and tumor cell motility. This pathway may reprogram mitochondrial dynamics to differentially adjust energy production or promote tumor cell invasion in response to microenvironment conditions.-Wang, Y., Agarwal, E., Bertolini, I., Ghosh, J. C., Seo, J. H., Altieri, D. C. IDH2 reprograms mitochondrial dynamics in cancer through a HIF-1α-regulated pseudohypoxic state.

Akt phosphorylation of mitochondrial Lonp1 protease enables oxidative metabolism and advanced tumor traits.

Tumor mitochondria have heightened protein folding quality control, but the regulators of this process and how they impact cancer traits are not completely understood. Here we show that the ATP-directed mitochondrial protease, LonP1 is upregulated by stress conditions, including hypoxia, in tumor, but not normal cells. In mitochondria, LonP1 is phosphorylated by Akt on Ser173 and Ser181, enhancing its protease activity. Interference with this pathway induces accumulation of misfolded subunits of electron transport chain complex II and complex V, resulting in impaired oxidative bioenergetics and heightened ROS production. Functionally, this suppresses mitochondrial trafficking to the cortical cytoskeleton, shuts off tumor cell migration and invasion, and inhibits primary and metastatic tumor growth, in vivo. These data identify LonP1 as a key effector of mitochondrial reprogramming in cancer and potential therapeutic target.

Regaining a Spatial Dimension: Mechanically Transferrable Two-Dimensional InAs Nanofins Grown by Selective Area Epitaxy.

We report a method for growing rectangular InAs nanofins with deterministic length, width, and height by dielectric-templated selective-area epitaxy. These freestanding nanofins can be transferred to lay flat on a separate substrate for device fabrication. A key goal was to regain a spatial dimension for device design compared to nanowires, while retaining the benefits of bottom-up epitaxial growth. The transferred nanofins were made into devices featuring multiple contacts for Hall effect and four-terminal resistance studies, as well as a global back-gate and nanoscale local top-gates for density control. Hall studies give a 3D electron density 2.5-5 × 1017 cm-3, corresponding to an approximate surface accumulation layer density 3-6 × 1012 cm-2 that agrees well with previous studies of InAs nanowires. We obtain Hall mobilities as high as 1200 cm2/(V s), field-effect mobilities as high as 4400 cm2/(V s), and clear quantum interference structure at temperatures as high as 20 K. Our devices show excellent prospects for fabrication into more complicated devices featuring multiple ohmic contacts, local gates, and possibly other functional elements, for example, patterned superconductor contacts, that may make them attractive options for future quantum information applications.